Purpose of This PDQ Summary
Overview
General Information
History
Laboratory/Animal/Preclinical Studies
Human/Clinical Studies
Adverse Effects
Overall Level of Evidence for Milk Thistle
Changes to This Summary (03/20/2008)
More Information

Purpose of This PDQ Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the use of milk thistle as a treatment for cancer. The summary is reviewed regularly and updated as necessary by the PDQ Cancer Complementary and Alternative Medicine Editorial Board ¹.

Information about the following is included in this summary:

• A brief history of milk thistle research.
• The results of clinical studies of milk thistle.
• Possible side effects of milk thistle use.

This summary is intended as a resource to inform and assist clinicians and other health professionals who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

Some of the reference citations in the summary are accompanied by a level of evidence designation. These designations are intended to help the readers assess the strength of the evidence supporting the use of specific interventions or treatment strategies. The PDQ Cancer Complementary and Alternative Medicine Editorial Board uses a formal evidence ranking system ² in developing its level of evidence designations. These designations should not be used as a basis for reimbursement determinations.

This summary is also available in a patient version ³, which is written in less technical language.

Overview

This complementary and alternative medicine (CAM) information summary provides an overview of the use of milk thistle as a treatment and adjunct agent in cancer therapy.

The summary includes a brief history of milk thistle, a review of the laboratory studies and clinical trials, and a description of adverse effects associated with milk thistle use.

This summary contains the following key information:

• Milk thistle is a plant whose fruit and seeds have been used for more than 2,000 years as a treatment for liver and biliary disorders.



• The active substance in milk thistle, silymarin, is a mixture of flavonolignans, primarily consisting of four isomers: silybin, isosilybin, silychristin (also known as silichristin), and silydianin (also known as silidianin). In the biological literature, silybin is referred to as silibinin.



• Laboratory studies demonstrate that silymarin functions as a potent antioxidant, stabilizes cellular membranes, stimulates detoxification pathways, stimulates regeneration of liver tissue, inhibits the growth of certain cancer cell lines, exerts direct cytotoxic activity toward certain cancer cell lines, and may increase the efficacy of certain chemotherapy agents.



• Human clinical trials have investigated milk thistle or silymarin primarily in individuals with hepatitis or cirrhosis. No clinical trials in individuals with cancer have been published.



• Few adverse side effects have been reported for milk thistle, but little information about interactions with anticancer medications or other drugs is available.



• Milk thistle is available in the United States as a dietary supplement.

Many of the medical and scientific terms used in the summary are hypertext linked (at first use in each section) to the NCI Dictionary ⁴, which is oriented toward nonexperts. When a linked term is clicked, a definition will appear in a separate window. All linked terms and their corresponding definitions will appear in a glossary in the printable version of the summary.

Reference citations in some PDQ CAM information summaries may include links to external Web sites that are operated by individuals or organizations for the purpose of marketing or advocating the use of specific treatments or products. These reference citations are included for informational purposes only. Their inclusion should not be viewed as an endorsement of the content of the Web sites, or of any treatment or product, by the PDQ Cancer CAM Editorial Board or the National Cancer Institute (NCI).

General Information

The botanical name for milk thistle is Silybum marianum (L.) Gaertn. Milk thistle is also referred to as holy thistle, Marian thistle, Mary thistle, Our Lady’s thistle, St. Mary thistle, wild artichoke, Mariendistel (German), and Chardon-Marie (French). The plant is indigenous to Europe but can also be found in the United States and South America. Traditionally, the leaves have been used in salads, and the fruit of the flower has been roasted as a coffee substitute. The seeds of milk thistle are the medicinal parts of the plant.[1] The primary active constituent of milk thistle is silymarin, which is composed of four isomers: silybin, isosilybin, silychristin, and silydianin. Most supplements are standardized according to their silybin content. In turn, silybin and isosilybin are both mixtures of two diastereomers, silybins A and B and isosilybins A and B, respectively.[2] Special formulations of silybin have been developed to enhance the bioavailability of the herbal product; these forms are sold under the names Legalon, silipide, and Siliphos. Because of milk thistle’s lipophilic nature, it is usually administered in capsule or tablet form rather than as an herbal tea. In Europe, silybin is administered intravenously as the only effective antidote for Amanita phalloides (Fr.) Link toxin.[3] Humans exposed to this mushroom toxin develop serious liver failure that ultimately progresses to death.

Several companies distribute milk thistle as a dietary supplement. In the United States, dietary supplements are regulated as foods, not drugs. Therefore, premarket evaluation and approval by the Food and Drug Administration (FDA) are not required unless specific disease prevention or treatment claims are made. Because dietary supplements are not formally reviewed for manufacturing consistency, ingredients may vary considerably from lot to lot; in addition, there is no guarantee that ingredients identified on product labels are present at all or are present in the specified amounts. It is important to note that the FDA has not approved the use of milk thistle as a treatment for cancer patients or patients with any other medical condition.

To conduct clinical drug research in the United States, researchers must file an Investigational New Drug (IND) application with the FDA. The IND application process is confidential, and IND information can be disclosed only by the applicants. To date, only one investigator has announced holding an IND to study milk thistle as an adjunct cancer treatment.

Despite milk thistle’s long history of being used to treat liver and biliary complaints, it was not until 1968 that silymarin was isolated from the seeds of the plant, and it was proposed that silymarin might be the active ingredient.[4] Silymarin was later determined to be a flavonolignan that is composed of four structurally similar compounds: silybin, isosilybin, silydianin, and silychristin.[2] Researchers have investigated the role that silibinin may play in the treatment of hepatitis and cirrhosis. Most studies have investigated the isolated compound silymarin or its most active isomer silybin, rather than the herbal plant in its whole form.

Silymarin is most well known for its purported effects on the liver. In laboratory studies, silymarin has been found to stabilize cell membranes, thus preventing toxic chemicals from entering the cell.[3,5-7] Laboratory studies have also demonstrated that silymarin stimulates synthesis and activity of enzymes responsible for detoxification pathways and exhibits potent antioxidant properties.[6-17] Specifically, silymarin has been shown to stimulate the glutathione S-transferase pathway and alter the intracellular concentration of glutathione (a potent antioxidant). Silymarin has also been shown to neutralize a wide range of free radicals.

Laboratory experiments conducted using cancer cell lines have suggested that silibinin enhances the efficacy of cisplatin and doxorubicin against ovarian and breast cancer cells.[18] Silybin appears to have direct anticancer effects against prostate, breast, and ectocervical tumor cells.[19] Silybin may also affect the cell cycle in cancer cells by slowing down cell growth, as demonstrated with prostate cancer cell lines.[20] Laboratory studies using leukemia cell lines found that silybin did not stimulate growth of leukemia cells.[21]

No human clinical trials on milk thistle or silymarin as a cancer treatment or as an adjunctive therapy in individuals with cancer have been published. Most clinical trials have investigated silymarin’s effectiveness in the treatment of patients with hepatitis, cirrhosis, or biliary disorders.[22-31] These studies have employed a wide range of doses (120–560 mg /day) and have yielded conflicting results. Many of the well-designed, large-scale trials have reported a beneficial effect rather than no effect. The most commonly reported adverse effects are a mild laxative effect and gastrointestinal upset.

References

1. PDR® for Herbal Medicines™. 2nd ed. Montvale, NJ: Medical Economics, 2000. 
   
   
2. Lee DY, Liu Y: Molecular structure and stereochemistry of silybin A, silybin B, isosilybin A, and isosilybin B, Isolated from Silybum marianum (milk thistle). J Nat Prod 66 (9): 1171-4, 2003.  [PUBMED Abstract]
   
   
3. Hruby K, Csomos G, Fuhrmann M, et al.: Chemotherapy of Amanita phalloides poisoning with intravenous silibinin. Hum Toxicol 2 (2): 183-95, 1983.  [PUBMED Abstract]
   
   
4. Wagner H, Hörhammer L, Münster R: [On the chemistry of silymarin (silybin), the active principle of the fruits from Silybum marianum (L.) Gaertn. (Carduus marianus L.)] Arzneimittelforschung 18 (6): 688-96, 1968.  [PUBMED Abstract]
   
   
5. Campos R, Garrido A, Guerra R, et al.: Silybin dihemisuccinate protects against glutathione depletion and lipid peroxidation induced by acetaminophen on rat liver. Planta Med 55 (5): 417-9, 1989.  [PUBMED Abstract]
   
   
6. Farghali H, Kameniková L, Hynie S, et al.: Silymarin effects on intracellular calcuim and cytotoxicity: a study in perfused rat hepatocytes after oxidative stress injury. Pharmacol Res 41 (2): 231-7, 2000.  [PUBMED Abstract]
   
   
7. Lettéron P, Labbe G, Degott C, et al.: Mechanism for the protective effects of silymarin against carbon tetrachloride-induced lipid peroxidation and hepatotoxicity in mice. Evidence that silymarin acts both as an inhibitor of metabolic activation and as a chain-breaking antioxidant. Biochem Pharmacol 39 (12): 2027-34, 1990.  [PUBMED Abstract]
   
   
8. Zhao J, Agarwal R: Tissue distribution of silibinin, the major active constituent of silymarin, in mice and its association with enhancement of phase II enzymes: implications in cancer chemoprevention. Carcinogenesis 20 (11): 2101-8, 1999.  [PUBMED Abstract]
   
   
9. Valenzuela A, Guerra R, Videla LA: Antioxidant properties of the flavonoids silybin and (+)-cyanidanol-3: comparison with butylated hydroxyanisole and butylated hydroxytoluene. Planta Med (6): 438-40, 1986.  [PUBMED Abstract]
   
   
10. Valenzuela A, Guerra R, Garrido A: Silybin dihemisuccinate protects rat erythrocytes against phenylhydrazine-induced lipid peroxidation and hemolysis. Planta Med 53 (5): 402-5, 1987.  [PUBMED Abstract]
    
    
11. Valenzuela A, Aspillaga M, Vial S, et al.: Selectivity of silymarin on the increase of the glutathione content in different tissues of the rat. Planta Med 55 (5): 420-2, 1989.  [PUBMED Abstract]
    
    
12. Mira ML, Azevedo MS, Manso C: The neutralization of hydroxyl radical by silibin, sorbinil and bendazac. Free Radic Res Commun 4 (2): 125-9, 1987.  [PUBMED Abstract]
    
    
13. Mira L, Silva M, Manso CF: Scavenging of reactive oxygen species by silibinin dihemisuccinate. Biochem Pharmacol 48 (4): 753-9, 1994.  [PUBMED Abstract]
    
    
14. Koch HP, Löffler E: Influence of silymarin and some flavonoids on lipid peroxidation in human platelets. Methods Find Exp Clin Pharmacol 7 (1): 13-8, 1985.  [PUBMED Abstract]
    
    
15. Garrido A, Arancibia C, Campos R, et al.: Acetaminophen does not induce oxidative stress in isolated rat hepatocytes: its probable antioxidant effect is potentiated by the flavonoid silybin. Pharmacol Toxicol 69 (1): 9-12, 1991.  [PUBMED Abstract]
    
    
16. Bosisio E, Benelli C, Pirola O: Effect of the flavanolignans of Silybum marianum L. on lipid peroxidation in rat liver microsomes and freshly isolated hepatocytes. Pharmacol Res 25 (2): 147-54, 1992 Feb-Mar.  [PUBMED Abstract]
    
    
17. Altorjay I, Dalmi L, Sári B, et al.: The effect of silibinin (Legalon) on the the free radical scavenger mechanisms of human erythrocytes in vitro. Acta Physiol Hung 80 (1-4): 375-80, 1992.  [PUBMED Abstract]
    
    
18. Scambia G, De Vincenzo R, Ranelletti FO, et al.: Antiproliferative effect of silybin on gynaecological malignancies: synergism with cisplatin and doxorubicin. Eur J Cancer 32A (5): 877-82, 1996.  [PUBMED Abstract]
    
    
19. Bhatia N, Zhao J, Wolf DM, et al.: Inhibition of human carcinoma cell growth and DNA synthesis by silibinin, an active constituent of milk thistle: comparison with silymarin. Cancer Lett 147 (1-2): 77-84, 1999.  [PUBMED Abstract]
    
    
20. Zi X, Agarwal R: Silibinin decreases prostate-specific antigen with cell growth inhibition via G1 arrest, leading to differentiation of prostate carcinoma cells: implications for prostate cancer intervention. Proc Natl Acad Sci U S A 96 (13): 7490-5, 1999.  [PUBMED Abstract]
    
    
21. Duthie SJ, Johnson W, Dobson VL: The effect of dietary flavonoids on DNA damage (strand breaks and oxidised pyrimdines) and growth in human cells. Mutat Res 390 (1-2): 141-51, 1997.  [PUBMED Abstract]
    
    
22. Vailati A, Aristia L, Sozzé E, et al.: Randomized open study of the dose-effect relationship of a short course of IdB 1016 in patients with viral or alcoholic hepatitis. Fitoterapia 64 (3), 219-28, 1993. 
    
    
23. Salmi HA, Sarna S: Effect of silymarin on chemical, functional, and morphological alterations of the liver. A double-blind controlled study. Scand J Gastroenterol 17 (4): 517-21, 1982.  [PUBMED Abstract]
    
    
24. Parés A, Planas R, Torres M, et al.: Effects of silymarin in alcoholic patients with cirrhosis of the liver: results of a controlled, double-blind, randomized and multicenter trial. J Hepatol 28 (4): 615-21, 1998.  [PUBMED Abstract]
    
    
25. Moscarella S, Giusti A, Marra F, et al.: Therapeutic and antilipoperoxidant effects of silybin-phosphatidylcholine complex in chronic liver disease: preliminary results. Current Therapeutic Research 53 (1): 98-102. 
    
    
26. Marena C, Lampertico M: Preliminary clinical development of silipide: a new complex of silybin in toxic liver disorders. Planta Med 57 (Suppl 2): A124-5, 1991. 
    
    
27. Marcelli R, Bizzoni P, Conte D, et al.: Randomized controlled study of the efficacy and tolerability of a short course of IdB 1016 in the treatment of chronic persistent hepatitis. European Bulletin of Drug Research 1 (3): 131-5, 1992. 
    
    
28. Flisiak R, Prokopowicz D: Effect of misoprostol on the course of viral hepatitis B. Hepatogastroenterology 44 (17): 1419-25, 1997 Sep-Oct.  [PUBMED Abstract]
    
    
29. Ferenci P: [Therapy of chronic hepatitis C] Wien Med Wochenschr 150 (23-24): 481-5, 2000.  [PUBMED Abstract]
    
    
30. Buzzelli G, Moscarella S, Giusti A, et al.: Therapeutic effects of a new silybin complex in chronic active hepatitis (CAH). [Abstract] Hellenic Journal of Gastroenterology 5 (Suppl): A-151, 38, 1992. 
    
    
31. Albrecht M, Frerick H, Kuhn U, et al.: Therapy of toxic liver pathologies with Legalon®. Z Klin Med 47: 87-92, 1992. 
    
    

History

Milk thistle has been used for more than 2,000 years, primarily as a treatment for liver dysfunction. The oldest reported use of milk thistle was by Dioscorides, who recommended the herb as a treatment for serpent bites.[1] Pliny the Elder (A.D. 23–79) reported that the juice of the plant mixed with honey is indicated for “carrying off bile.”[1,2] In the Middle Ages, milk thistle was revered as an antidote for liver toxins.[1,2] The British herbalist Culpepper reported it to be effective for relieving obstructions of the liver.[1,2] In 1898, eclectic physicians Felter and Lloyd stated the herb was good for congestion of the liver, spleen, and kidney.[1,2] Native Americans use milk thistle to treat boils and other skin diseases. Homeopathic practitioners used preparations from the seeds to treat jaundice, gallstones, peritonitis, hemorrhage, bronchitis, and varicose veins.[2] The German Commission E recommends milk thistle use for dyspeptic complaints, toxin-induced liver damage, hepatic cirrhosis, and as a supportive therapy for chronic inflammatory liver conditions.[3]

References

1. Flora K, Hahn M, Rosen H, et al.: Milk thistle (Silybum marianum) for the therapy of liver disease. Am J Gastroenterol 93 (2): 139-43, 1998.  [PUBMED Abstract]
   
   
2. Foster S: Milk Thistle: Silybum marianum. Rev. ed. Austin, Tex: American Botanical Council, 1999. 
   
   
3. Blumenthal M, Busse WR, et al., eds.: The Complete German Commission E Monographs: Therapeutic Guide to Herbal Medicines. Austin, Tex: American Botanical Council, 1998. 
   
   

Laboratory/Animal/Preclinical Studies

Research studies conducted in the laboratory have investigated the properties of silymarin or its isomer silybin using cell lines and animal models. Other substances in milk thistle have not been extensively studied.

Several research studies have investigated the effects of silymarin or silybin in a noncancer context. These studies have tested silymarin or silybin:

• In healthy animal liver and kidney cells.
• As a prophylaxis against toxic chemicals.
• In stimulating detoxification pathways (enzyme concentrations and activity).
• For antioxidant properties.

Silymarin or silybin has also been investigated in cancer models. The effects of silymarin and/or silybin have been investigated in prostate (DU 145, LNCaP, PC-3),[1-5] breast (MDA-MB 468, MCF-7),[6-8] hepatic (HepG2),[9,10] epidermoid (A431),[10] colon (Caco-2),[11] ovarian (OVCA 433, A2780),[12] histiocytic lymphoma (U-937),[13] and leukemia (HL-60) [14,15] cells. In animal tumor models, tongue cancer,[16] skin cancer,[17-22] bladder cancer,[23] and adenocarcinoma of the colon [24,25] and small intestine [25] have been investigated. These studies have tested the ability of silymarin or silibinin to:

• Mitigate the toxicity associated with chemotherapy agents.
• Enhance the efficacy of chemotherapy agents.
• Inhibit the growth of cancer cell lines and inhibit tumor initiation or tumor promotion.

Although many of these studies have produced encouraging results, none of the findings have been replicated in human clinical trials.

Laboratory data suggest that silymarin and silybin protect the liver from damage induced by toxic chemicals. Animal studies have found that liver cells treated with silybin and then exposed to toxins do not incur cell damage or death at the same rate as liver cells that are not treated with silybin. This finding suggests that silybin can prevent toxins from entering the cell or effectively exports toxins out of the cell before damage ensues.[10,26-30] Alternatively, this may be related to the effect of silymarin on detoxification systems. In vitro data have shown silybin to stimulate and/or inhibit phase I detoxification pathways in silybin-treated human liver cells. However, this effect was found to be dose-dependent, and these levels are not physiologically attainable with the current manufacturer dose recommendations.[31,32]

Silymarin has been shown to stimulate phase II detoxification pathways in mice. Administration of silymarin (100 or 200 mg /kg body weight/day) to SENCAR mice for 3 days significantly increased glutathione S-transferase activity in the liver (P < .01–.001), lung (P < .05–.01), stomach (P < .05), small bowel (P < .01), and skin (P < .01). This effect appeared to be dose-dependent.[33] Administration of silymarin to rats challenged with a toxin (50 mg/kg body weight) resulted in higher levels of glutathione in liver cells, decreased levels of oxidative stress (measured by malondialdehyde concentrations), and less elevated liver function tests (measured by levels of aspartate aminotransferase [AST] and alanine aminotransferase [ALT]).[30] Silymarin and silybin have also been found to accelerate cell regeneration in the liver through stimulation of precursors to DNA synthesis and enhancement of production of the cellular enzymes required for synthesis of DNA.[34-39] Laboratory studies have also shown silymarin and silybin to be potent antioxidants.[27,28,40-47] Silymarin has been shown to mitigate oxidative stress in cells treated with pro-oxidant compounds.

A number of laboratory studies have investigated the effect of silymarin or silybin on the efficacy and toxicity of chemotherapy agents or have measured their direct cytotoxic activity. In an investigation of the effect of a variety of flavonoids on the formation of DNA damage, silymarin did not induce DNA damage in colon (Caco-2) cells, hepatoma (HepG2) cells, and human lymphocytes.[11] At higher concentrations of silymarin (400–1,000 μmol/L) DNA damage was induced in an epithelial cell line (HeLa cells). At higher concentrations (1,000 μmol/L) DNA damage was observed in human lymphocytes. Cell growth was inhibited as the flavonoid concentration was increased in human lymphocytes and HeLa cells. Only at very high concentrations was cell viability affected by silymarin in HepG2 cells. Although this study demonstrated that the flavonolignans of Silybum marianum (L.) are capable of inhibiting cellular proliferation and inducing DNA strand breaks, the results were obtained at very high concentrations that may be difficult to achieve in humans. This study also showed that silymarin does not stimulate cell growth in the HeLa, Burkitt lymphoma, and human hepatoma cell lines.

Silymarin has also been investigated as a possible adjunctive agent in mitigating some of the toxicity associated with chemotherapy agents. Silybin and silychristin exerted a protective effect on monkey kidney cells exposed to vincristine and especially cisplatin chemotherapy.[48] Silybin (200 mg/kg body weight) administration with cisplatin in rats resulted in statistically significant reductions in measures of kidney toxicity.[49] Significant decreases in weight loss, faster recovery of urinary osmolality measures, and depressions in the increase in activity of urinary alanine aminopeptidase ([AAP], a marker of kidney toxicity) were observed. Silybin had no effect on magnesium excretion or glomerular function. Silybin (2 g /kg body weight) administration in rats receiving cisplatin prevented reductions in creatinine clearance, increases in urea plasma levels, and large increases in urinary AAP.[50] No effect on magnesium excretion was observed. Silybin did not interfere with the antineoplastic effects of cisplatin or ifosfamide in germ cell tumors. In experiments with ovarian and breast cancer cell lines, silybin potentiated the effect of cisplatin and doxorubicin.[12] IdB 1,016, a form of silybin bound to a phospholipid complex, was found to enhance the activity of cisplatin against A2780 ovarian cancer cells but had no effect on its own.[51] Silybin increased the chemosensitivity of DU 145 prostate cancer cells resistant to chemotherapy.[52]

Studies have also investigated the effect of silymarin on tumor initiation and promotion. Silymarin appears to have a chemopreventive effect through perturbations in the cell cycle, altering cell signaling that induces cellular proliferation, affecting angiogenesis, or through its anti-inflammatory properties.[1,6,12,18,53] These findings have been supported in human prostate, breast, ectocervical, ovarian, hepatic, leukemia, and epidermoid cell lines.[4,6,8,9,14,54] An investigation of the effect of silymarin on ultraviolet B radiation-induced nonmelanoma skin cancer in mice found that silymarin treatment significantly reduced tumor incidence (P < .003), tumor multiplicity (P < .0001), and tumor volume (P < .0001).[18] These findings suggest that silymarin plays a prominent role in the reduction of cancer cells and in preventing the formation of cancer cells. A number of studies have investigated the mechanism through, which silymarin may affect tumor promotion in mouse skin tumor models. Studies have found that silymarin reduces transcription of markers of tumor promotion and activity,[18] inhibits transcription of tumor promoters,[55] stimulates antioxidant activities,[18,22] interferes with cell signaling,[54] inhibits inflammatory actions,[18,21] and modulates cell-cycle regulation.[56]

In prostate cancer cell lines, silybin has been shown to inhibit growth factors and stimulate cell growth,[1-3,5] promote cell cycle arrest,[1,4] and inhibit antiapoptotic activity.[52] In rats with azoxymethane -induced colon cancer, dietary silymarin resulted in a reduction in the incidence and multiplicity of adenocarcinoma of the colon in a dose-dependent manner.[24,25] Dietary silymarin had no effect on small intestinal adenocarcinoma,[25] but exerted a preventive effect in mice with N-butyl-N-(4-hydroxybutyl) nitrosamine –induced bladder cancer [23] and in F344 rats with 4-nitroquinoline 1-oxide –induced cancer of the tongue.[16] Dietary silybin administered to nude mice with prostate carcinoma increased production of insulin-like growth factor-binding protein-3 in the plasma of mice and significantly inhibited tumor volume (P < .05).[2]

References

1. Zi X, Agarwal R: Silibinin decreases prostate-specific antigen with cell growth inhibition via G1 arrest, leading to differentiation of prostate carcinoma cells: implications for prostate cancer intervention. Proc Natl Acad Sci U S A 96 (13): 7490-5, 1999.  [PUBMED Abstract]
   
   
2. Singh RP, Dhanalakshmi S, Tyagi AK, et al.: Dietary feeding of silibinin inhibits advance human prostate carcinoma growth in athymic nude mice and increases plasma insulin-like growth factor-binding protein-3 levels. Cancer Res 62 (11): 3063-9, 2002.  [PUBMED Abstract]
   
   
3. Zi X, Zhang J, Agarwal R, et al.: Silibinin up-regulates insulin-like growth factor-binding protein 3 expression and inhibits proliferation of androgen-independent prostate cancer cells. Cancer Res 60 (20): 5617-20, 2000.  [PUBMED Abstract]
   
   
4. Zi X, Grasso AW, Kung HJ, et al.: A flavonoid antioxidant, silymarin, inhibits activation of erbB1 signaling and induces cyclin-dependent kinase inhibitors, G1 arrest, and anticarcinogenic effects in human prostate carcinoma DU145 cells. Cancer Res 58 (9): 1920-9, 1998.  [PUBMED Abstract]
   
   
5. Sharma Y, Agarwal C, Singh AK, et al.: Inhibitory effect of silibinin on ligand binding to erbB1 and associated mitogenic signaling, growth, and DNA synthesis in advanced human prostate carcinoma cells. Mol Carcinog 30 (4): 224-36, 2001.  [PUBMED Abstract]
   
   
6. Bhatia N, Zhao J, Wolf DM, et al.: Inhibition of human carcinoma cell growth and DNA synthesis by silibinin, an active constituent of milk thistle: comparison with silymarin. Cancer Lett 147 (1-2): 77-84, 1999.  [PUBMED Abstract]
   
   
7. Jiang C, Agarwal R, Lü J: Anti-angiogenic potential of a cancer chemopreventive flavonoid antioxidant, silymarin: inhibition of key attributes of vascular endothelial cells and angiogenic cytokine secretion by cancer epithelial cells. Biochem Biophys Res Commun 276 (1): 371-8, 2000.  [PUBMED Abstract]
   
   
8. Zi X, Feyes DK, Agarwal R: Anticarcinogenic effect of a flavonoid antioxidant, silymarin, in human breast cancer cells MDA-MB 468: induction of G1 arrest through an increase in Cip1/p21 concomitant with a decrease in kinase activity of cyclin-dependent kinases and associated cyclins. Clin Cancer Res 4 (4): 1055-64, 1998.  [PUBMED Abstract]
   
   
9. Saliou C, Rihn B, Cillard J, et al.: Selective inhibition of NF-kappaB activation by the flavonoid hepatoprotector silymarin in HepG2. Evidence for different activating pathways. FEBS Lett 440 (1-2): 8-12, 1998.  [PUBMED Abstract]
   
   
10. Shear NH, Malkiewicz IM, Klein D, et al.: Acetaminophen-induced toxicity to human epidermoid cell line A431 and hepatoblastoma cell line Hep G2, in vitro, is diminished by silymarin. Skin Pharmacol 8 (6): 279-91, 1995.  [PUBMED Abstract]
    
    
11. Duthie SJ, Johnson W, Dobson VL: The effect of dietary flavonoids on DNA damage (strand breaks and oxidised pyrimdines) and growth in human cells. Mutat Res 390 (1-2): 141-51, 1997.  [PUBMED Abstract]
    
    
12. Scambia G, De Vincenzo R, Ranelletti FO, et al.: Antiproliferative effect of silybin on gynaecological malignancies: synergism with cisplatin and doxorubicin. Eur J Cancer 32A (5): 877-82, 1996.  [PUBMED Abstract]
    
    
13. Manna SK, Mukhopadhyay A, Van NT, et al.: Silymarin suppresses TNF-induced activation of NF-kappa B, c-Jun N-terminal kinase, and apoptosis. J Immunol 163 (12): 6800-9, 1999.  [PUBMED Abstract]
    
    
14. Kang SN, Lee MH, Kim KM, et al.: Induction of human promyelocytic leukemia HL-60 cell differentiation into monocytes by silibinin: involvement of protein kinase C. Biochem Pharmacol 61 (12): 1487-95, 2001.  [PUBMED Abstract]
    
    
15. Clinton SK: The dietary antioxidant network and prostate carcinoma. Cancer 86 (9): 1629-31, 1999.  [PUBMED Abstract]
    
    
16. Yanaida Y, Kohno H, Yoshida K, et al.: Dietary silymarin suppresses 4-nitroquinoline 1-oxide-induced tongue carcinogenesis in male F344 rats. Carcinogenesis 23 (5): 787-94, 2002.  [PUBMED Abstract]
    
    
17. Agarwal R, Katiyar SK, Lundgren DW, et al.: Inhibitory effect of silymarin, an anti-hepatotoxic flavonoid, on 12-O-tetradecanoylphorbol-13-acetate-induced epidermal ornithine decarboxylase activity and mRNA in SENCAR mice. Carcinogenesis 15 (6): 1099-103, 1994.  [PUBMED Abstract]
    
    
18. Katiyar SK, Korman NJ, Mukhtar H, et al.: Protective effects of silymarin against photocarcinogenesis in a mouse skin model. J Natl Cancer Inst 89 (8): 556-66, 1997.  [PUBMED Abstract]
    
    
19. Lahiri-Chatterjee M, Katiyar SK, Mohan RR, et al.: A flavonoid antioxidant, silymarin, affords exceptionally high protection against tumor promotion in the SENCAR mouse skin tumorigenesis model. Cancer Res 59 (3): 622-32, 1999.  [PUBMED Abstract]
    
    
20. Singh RP, Tyagi AK, Zhao J, et al.: Silymarin inhibits growth and causes regression of established skin tumors in SENCAR mice via modulation of mitogen-activated protein kinases and induction of apoptosis. Carcinogenesis 23 (3): 499-510, 2002.  [PUBMED Abstract]
    
    
21. Zhao J, Sharma Y, Agarwal R: Significant inhibition by the flavonoid antioxidant silymarin against 12-O-tetradecanoylphorbol 13-acetate-caused modulation of antioxidant and inflammatory enzymes, and cyclooxygenase 2 and interleukin-1alpha expression in SENCAR mouse epidermis: implications in the prevention of stage I tumor promotion. Mol Carcinog 26 (4): 321-33, 1999.  [PUBMED Abstract]
    
    
22. Zhao J, Lahiri-Chatterjee M, Sharma Y, et al.: Inhibitory effect of a flavonoid antioxidant silymarin on benzoyl peroxide-induced tumor promotion, oxidative stress and inflammatory responses in SENCAR mouse skin. Carcinogenesis 21 (4): 811-6, 2000.  [PUBMED Abstract]
    
    
23. Vinh PQ, Sugie S, Tanaka T, et al.: Chemopreventive effects of a flavonoid antioxidant silymarin on N-butyl-N-(4-hydroxybutyl)nitrosamine-induced urinary bladder carcinogenesis in male ICR mice. Jpn J Cancer Res 93 (1): 42-9, 2002.  [PUBMED Abstract]
    
    
24. Kohno H, Tanaka T, Kawabata K, et al.: Silymarin, a naturally occurring polyphenolic antioxidant flavonoid, inhibits azoxymethane-induced colon carcinogenesis in male F344 rats. Int J Cancer 101 (5): 461-8, 2002.  [PUBMED Abstract]
    
    
25. Gershbein LL: Action of dietary trypsin, pressed coffee oil, silymarin and iron salt on 1,2-dimethylhydrazine tumorigenesis by gavage. Anticancer Res 14 (3A): 1113-6, 1994 May-Jun.  [PUBMED Abstract]
    
    
26. Campos R, Garrido A, Guerra R, et al.: Silybin dihemisuccinate protects against glutathione depletion and lipid peroxidation induced by acetaminophen on rat liver. Planta Med 55 (5): 417-9, 1989.  [PUBMED Abstract]
    
    
27. Farghali H, Kameniková L, Hynie S, et al.: Silymarin effects on intracellular calcuim and cytotoxicity: a study in perfused rat hepatocytes after oxidative stress injury. Pharmacol Res 41 (2): 231-7, 2000.  [PUBMED Abstract]
    
    
28. Lettéron P, Labbe G, Degott C, et al.: Mechanism for the protective effects of silymarin against carbon tetrachloride-induced lipid peroxidation and hepatotoxicity in mice. Evidence that silymarin acts both as an inhibitor of metabolic activation and as a chain-breaking antioxidant. Biochem Pharmacol 39 (12): 2027-34, 1990.  [PUBMED Abstract]
    
    
29. Valenzuela A, Guerra R, Garrido A: Silybin dihemisuccinate protects rat erythrocytes against phenylhydrazine-induced lipid peroxidation and hemolysis. Planta Med 53 (5): 402-5, 1987.  [PUBMED Abstract]
    
    
30. Campos R, Garrido A, Guerra R, et al.: Acetaminophen hepatotoxicity in rats is attenuated by silybin dihemisuccinate. Prog Clin Biol Res 280: 375-8, 1988.  [PUBMED Abstract]
    
    
31. Zuber R, Modrianský M, Dvorák Z, et al.: Effect of silybin and its congeners on human liver microsomal cytochrome P450 activities. Phytother Res 16 (7): 632-8, 2002.  [PUBMED Abstract]
    
    
32. Venkataramanan R, Ramachandran V, Komoroski BJ, et al.: Milk thistle, a herbal supplement, decreases the activity of CYP3A4 and uridine diphosphoglucuronosyl transferase in human hepatocyte cultures. Drug Metab Dispos 28 (11): 1270-3, 2000.  [PUBMED Abstract]
    
    
33. Zhao J, Agarwal R: Tissue distribution of silibinin, the major active constituent of silymarin, in mice and its association with enhancement of phase II enzymes: implications in cancer chemoprevention. Carcinogenesis 20 (11): 2101-8, 1999.  [PUBMED Abstract]
    
    
34. Sonnenbichler J, Mattersberger J, Rosen H: [Stimulation of RNA synthesis in rat liver and isolated hepatocytes by silybin, an antihepatotoxic agent from Silybum marianum L. Gaertn (author's transl)] Hoppe Seylers Z Physiol Chem 357 (8): 1171-80, 1976.  [PUBMED Abstract]
    
    
35. Sonnenbichler J, Zetl I: [Mechanism of action of silibinin. V. Effect of silibinin on the synthesis of ribosomal RNA, mRNA and tRNA in rat liver in vivo] Hoppe Seylers Z Physiol Chem 365 (5): 555-66, 1984.  [PUBMED Abstract]
    
    
36. Sonnenbichler J, Zetl I: Biochemical effects of the flavonolignane silibinin on RNA, protein and DNA synthesis in rat livers. Prog Clin Biol Res 213: 319-31, 1986.  [PUBMED Abstract]
    
    
37. Sonnenbichler J, Goldberg M, Hane L, et al.: Stimulatory effect of Silibinin on the DNA synthesis in partially hepatectomized rat livers: non-response in hepatoma and other malign cell lines. Biochem Pharmacol 35 (3): 538-41, 1986.  [PUBMED Abstract]
    
    
38. Machicao F, Sonnenbichler J: Mechanism of the stimulation of RNA synthesis in rat liver nuclei by silybin. Hoppe Seylers Z Physiol Chem 358 (2): 141-7, 1977.  [PUBMED Abstract]
    
    
39. Dehmlow C, Erhard J, de Groot H: Inhibition of Kupffer cell functions as an explanation for the hepatoprotective properties of silibinin. Hepatology 23 (4): 749-54, 1996.  [PUBMED Abstract]
    
    
40. Valenzuela A, Guerra R, Videla LA: Antioxidant properties of the flavonoids silybin and (+)-cyanidanol-3: comparison with butylated hydroxyanisole and butylated hydroxytoluene. Planta Med (6): 438-40, 1986.  [PUBMED Abstract]
    
    
41. Valenzuela A, Aspillaga M, Vial S, et al.: Selectivity of silymarin on the increase of the glutathione content in different tissues of the rat. Planta Med 55 (5): 420-2, 1989.  [PUBMED Abstract]
    
    
42. Mira ML, Azevedo MS, Manso C: The neutralization of hydroxyl radical by silibin, sorbinil and bendazac. Free Radic Res Commun 4 (2): 125-9, 1987.  [PUBMED Abstract]
    
    
43. Mira L, Silva M, Manso CF: Scavenging of reactive oxygen species by silibinin dihemisuccinate. Biochem Pharmacol 48 (4): 753-9, 1994.  [PUBMED Abstract]
    
    
44. Koch HP, Löffler E: Influence of silymarin and some flavonoids on lipid peroxidation in human platelets. Methods Find Exp Clin Pharmacol 7 (1): 13-8, 1985.  [PUBMED Abstract]
    
    
45. Garrido A, Arancibia C, Campos R, et al.: Acetaminophen does not induce oxidative stress in isolated rat hepatocytes: its probable antioxidant effect is potentiated by the flavonoid silybin. Pharmacol Toxicol 69 (1): 9-12, 1991.  [PUBMED Abstract]
    
    
46. Bosisio E, Benelli C, Pirola O: Effect of the flavanolignans of Silybum marianum L. on lipid peroxidation in rat liver microsomes and freshly isolated hepatocytes. Pharmacol Res 25 (2): 147-54, 1992 Feb-Mar.  [PUBMED Abstract]
    
    
47. Altorjay I, Dalmi L, Sári B, et al.: The effect of silibinin (Legalon) on the the free radical scavenger mechanisms of human erythrocytes in vitro. Acta Physiol Hung 80 (1-4): 375-80, 1992.  [PUBMED Abstract]
    
    
48. Sonnenbichler J, Scalera F, Sonnenbichler I, et al.: Stimulatory effects of silibinin and silicristin from the milk thistle Silybum marianum on kidney cells. J Pharmacol Exp Ther 290 (3): 1375-83, 1999.  [PUBMED Abstract]
    
    
49. Gaedeke J, Fels LM, Bokemeyer C, et al.: Cisplatin nephrotoxicity and protection by silibinin. Nephrol Dial Transplant 11 (1): 55-62, 1996.  [PUBMED Abstract]
    
    
50. Bokemeyer C, Fels LM, Dunn T, et al.: Silibinin protects against cisplatin-induced nephrotoxicity without compromising cisplatin or ifosfamide anti-tumour activity. Br J Cancer 74 (12): 2036-41, 1996.  [PUBMED Abstract]
    
    
51. Giacomelli S, Gallo D, Apollonio P, et al.: Silybin and its bioavailable phospholipid complex (IdB 1016) potentiate in vitro and in vivo the activity of cisplatin. Life Sci 70 (12): 1447-59, 2002.  [PUBMED Abstract]
    
    
52. Dhanalakshmi S, Singh RP, Agarwal C, et al.: Silibinin inhibits constitutive and TNFalpha-induced activation of NF-kappaB and sensitizes human prostate carcinoma DU145 cells to TNFalpha-induced apoptosis. Oncogene 21 (11): 1759-67, 2002.  [PUBMED Abstract]
    
    
53. Zi X, Agarwal R: Modulation of mitogen-activated protein kinase activation and cell cycle regulators by the potent skin cancer preventive agent silymarin. Biochem Biophys Res Commun 263 (2): 528-36, 1999.  [PUBMED Abstract]
    
    
54. Ahmad N, Gali H, Javed S, et al.: Skin cancer chemopreventive effects of a flavonoid antioxidant silymarin are mediated via impairment of receptor tyrosine kinase signaling and perturbation in cell cycle progression. Biochem Biophys Res Commun 247 (2): 294-301, 1998.  [PUBMED Abstract]
    
    
55. Zi X, Mukhtar H, Agarwal R: Novel cancer chemopreventive effects of a flavonoid antioxidant silymarin: inhibition of mRNA expression of an endogenous tumor promoter TNF alpha. Biochem Biophys Res Commun 239 (1): 334-9, 1997.  [PUBMED Abstract]
    
    
56. Singh RP, Agarwal R: Flavonoid antioxidant silymarin and skin cancer. Antioxid Redox Signal 4 (4): 655-63, 2002.  [PUBMED Abstract]
    
    

Human/Clinical Studies

There are no published clinical trials of milk thistle or silymarin in patients with cancer. Two published case reports describe the use of milk thistle as either a treatment or an adjunctive therapy in individuals with cancer. One case report describes the use of milk thistle in a 34-year-old woman with promyelocytic leukemia.[1] The investigators administered 800 mg of silymarin during the patient’s maintenance therapy, which consisted of treatment with methotrexate and 6-mercaptopurine. During the 4 months of treatment with silymarin, the patient who previously required intermittent breaks in therapy due to abnormal liver enzyme levels had normal liver enzyme levels with no further interruption of therapy. A second case report describes a 52-year-old man with hepatocellular carcinoma.[2] The patient began taking 450 mg of silymarin per day, and spontaneous regression of the tumor was reported in the absence of initiation of anticancer therapy. These findings have not been reproduced in a clinical trial.

Most clinical trials of milk thistle have been conducted in patients with either hepatitis or cirrhosis. Other studies have investigated milk thistle in patients with hyperlipidemia, diabetes, and Amanita phalloides mushroom poisoning. Eight randomized trials [3-10] have been reported in patients with hepatitis or cirrhosis, and one randomized trial has reported the use of silymarin as a prophylaxis to iatrogenic hepatic toxicity.[11] Endpoints for these trials have included serum levels of bilirubin and/or the liver enzymes aspartate aminotransferase (AST) and alanine aminotransferase (ALT), as higher levels are an indicator of liver inflammation, damage, or disease. The lowering of these serum levels is a sign of an improving condition. In patients with hepatitis A and B, one clinical trial found silymarin (140 mg daily for 3–4 weeks) resulting in lower levels of AST, ALT, and bilirubin by day 5, compared with a placebo group.[12] In another randomized, placebo-controlled study of patients with viral hepatitis B, silymarin (210 mg daily) had no effect on course of disease or enzyme levels.[6]

In patients with chronic liver disease, a randomized, placebo-controlled study found normalization of serum AST, ALT, and bilirubin levels after 1 month of treatment with silymarin (140 mg 3 times a day) in comparison to treatment with a placebo.[13] In one of the largest observational studies involving 2,637 patients with chronic liver disease, 8-week treatment with 560 mg/day of silymarin resulted in reductions of serum AST, ALT, and gamma-glutamyltranspeptidase ([GGT], a marker of bile duct disease) and a decrease in the frequency of palpable hepatomegaly.[14]

Another published report describes the use of silybin as the only effective antidote in patients with liver damage from Amanita phalloides (Fr.) Link poisoning.[15] Patients were administered doses of 35 to 55 mg/kg body weight, with no reports of adverse events. A recent retrospective review of the treatment for Amanita phalloides poisoning suggests that silymarin continues to be a promising drug in the treatment of this rare mushroom poisoning.[16] The beneficial effect of silymarin on liver histology suggests it has a role in the prevention of hepatitis and/or hepatocellular carcinoma; however, no clinical trials in humans have investigated the use of silymarin for prevention.

References

1. Invernizzi R, Bernuzzi S, Ciani D, et al.: Silymarine during maintenance therapy of acute promyelocytic leukemia. Haematologica 78 (5): 340-1, 1993 Sep-Oct.  [PUBMED Abstract]
   
   
2. Grossmann M, Hoermann R, Weiss M, et al.: Spontaneous regression of hepatocellular carcinoma. Am J Gastroenterol 90 (9): 1500-3, 1995.  [PUBMED Abstract]
   
   
3. Vailati A, Aristia L, Sozzé E, et al.: Randomized open study of the dose-effect relationship of a short course of IdB 1016 in patients with viral or alcoholic hepatitis. Fitoterapia 64 (3), 219-28, 1993. 
   
   
4. Salmi HA, Sarna S: Effect of silymarin on chemical, functional, and morphological alterations of the liver. A double-blind controlled study. Scand J Gastroenterol 17 (4): 517-21, 1982.  [PUBMED Abstract]
   
   
5. Parés A, Planas R, Torres M, et al.: Effects of silymarin in alcoholic patients with cirrhosis of the liver: results of a controlled, double-blind, randomized and multicenter trial. J Hepatol 28 (4): 615-21, 1998.  [PUBMED Abstract]
   
   
6. Flisiak R, Prokopowicz D: Effect of misoprostol on the course of viral hepatitis B. Hepatogastroenterology 44 (17): 1419-25, 1997 Sep-Oct.  [PUBMED Abstract]
   
   
7. Angulo P, Patel T, Jorgensen RA, et al.: Silymarin in the treatment of patients with primary biliary cirrhosis with a suboptimal response to ursodeoxycholic acid. Hepatology 32 (5): 897-900, 2000.  [PUBMED Abstract]
   
   
8. Ferenci P, Dragosics B, Dittrich H, et al.: Randomized controlled trial of silymarin treatment in patients with cirrhosis of the liver. J Hepatol 9 (1): 105-13, 1989.  [PUBMED Abstract]
   
   
9. Lucena MI, Andrade RJ, de la Cruz JP, et al.: Effects of silymarin MZ-80 on oxidative stress in patients with alcoholic cirrhosis. Results of a randomized, double-blind, placebo-controlled clinical study. Int J Clin Pharmacol Ther 40 (1): 2-8, 2002.  [PUBMED Abstract]
   
   
10. Velussi M, Cernigoi AM, De Monte A, et al.: Long-term (12 months) treatment with an anti-oxidant drug (silymarin) is effective on hyperinsulinemia, exogenous insulin need and malondialdehyde levels in cirrhotic diabetic patients. J Hepatol 26 (4): 871-9, 1997.  [PUBMED Abstract]
    
    
11. Palasciano G, Portincasa P, Palmieri V, et al.: The effect of silymarin on plasma levels of malon-dialdehyde in patients receiving long-term treatment with psychotropic drugs. Current Therapeutic Research 55 (5): 537-45. 
    
    
12. Magliulo E, Gagliardi B, Fiori GP: [Results of a double blind study on the effect of silymarin in the treatment of acute viral hepatitis, carried out at two medical centres (author's transl)] Med Klin 73 (28-29): 1060-5, 1978.  [PUBMED Abstract]
    
    
13. Trinchet JC, Beaugrand M, Callard P, et al.: Treatment of alcoholic hepatitis with colchicine. Results of a randomized double blind trial. Gastroenterol Clin Biol 13 (6-7): 551-5, 1989.  [PUBMED Abstract]
    
    
14. Albrecht M, Frerick H, Kuhn U, et al.: Therapy of toxic liver pathologies with Legalon®. Z Klin Med 47: 87-92, 1992. 
    
    
15. Hruby K, Csomos G, Fuhrmann M, et al.: Chemotherapy of Amanita phalloides poisoning with intravenous silibinin. Hum Toxicol 2 (2): 183-95, 1983.  [PUBMED Abstract]
    
    
16. Enjalbert F, Rapior S, Nouguier-Soulé J, et al.: Treatment of amatoxin poisoning: 20-year retrospective analysis. J Toxicol Clin Toxicol 40 (6): 715-57, 2002.  [PUBMED Abstract]
    
    

Adverse Effects

Human studies of silymarin have shown minimal adverse effects in multiple large, blinded, placebo-controlled, randomized studies. Silymarin is well tolerated, with only rare reports of a mild laxative effect. Mild allergic reactions have been seen at high doses (>1,500 mg /day), although the details of these allergic reactions were not reported.[1] A recent case report from Australia described a reaction to a milk thistle extract that included intermittent episodes of sweating, abdominal cramping, nausea, vomiting, diarrhea, and weakness.[2] All symptoms resolved when the silymarin was discontinued. The authors suggested that the capsules were contaminated; the type of contamination was unknown.

According to the German Commission E, there are no reported side effects with milk thistle within the recommended doses. Rare cases of milk thistle having a laxative effect have been reported. Human studies have reported stomach upset, heartburn, and transient headaches; however, none of these symptoms were attributed to supplementation with milk thistle, and supplementation was not discontinued.[3] One human dosing study reported nausea, heartburn, and dyspepsia in patients treated with 160 mg/day, dyspepsia in patients treated with 240 mg/day, and postprandial nausea and meteorism in patients treated with 360 mg/day. None of these side effects were dose related.

Silymarin has been well tolerated in high doses. Silymarin has been used in pregnant women with intrahepatic cholestasis at doses of 560 mg/day for 16 days, with no toxicity to the patient or the fetus.[4] The published data on silymarin use in children focuses on intravenous doses of 20 to 50 mg/kg body weight for mushroom poisoning.[5] Silymarin has also proved nontoxic in rats and mice when administered in doses as high as 5,000 mg/kg body weight. Rats and dogs have received silymarin at doses of 50 to 2,500 mg/kg body weight for a 12-month period. Investigations, including postmortem analyses, showed no evidence of toxicity.

It is not known whether milk thistle may reduce, enhance, or have no effect on the effectiveness of chemotherapy. Silymarin decreases the activity of the cytochrome P450 enzyme system, which is involved in the clearance of certain chemotherapy drugs.[6] However, the dose at which inhibition is observed is high and not achieved with oral intake of silymarin.[7] Milk thistle may also interact adversely with chemotherapy drugs that exert their cytotoxic effects through generation of free radicals. Silymarin and its metabolite inhibit P-glycoprotein-mediated cellular efflux, leading to potentiation of doxorubicin cytotoxicity.[8] No trials have been performed to support or negate these theoretical considerations. No effects on indinavir and alcohol pharmacokinetics has been observed. Enhancement of antiarrhythmic effects of amiodarone in rats has been observed.[8]

References

1. PDR® for Herbal Medicines™. 2nd ed. Montvale, NJ: Medical Economics, 2000. 
   
   
2. An adverse reaction to the herbal medication milk thistle (Silybum marianum). Adverse Drug Reactions Advisory Committee. Med J Aust 170 (5): 218-9, 1999.  [PUBMED Abstract]
   
   
3. Vailati A, Aristia L, Sozzé E, et al.: Randomized open study of the dose-effect relationship of a short course of IdB 1016 in patients with viral or alcoholic hepatitis. Fitoterapia 64 (3), 219-28, 1993. 
   
   
4. Hernández R, Nazar E: [Effect of silymarin in intrahepatic cholestasis of pregnancy (preliminary communication)] Rev Chil Obstet Ginecol 47 (1): 22-9, 1982.  [PUBMED Abstract]
   
   
5. Hruby K, Csomos G, Fuhrmann M, et al.: Chemotherapy of Amanita phalloides poisoning with intravenous silibinin. Hum Toxicol 2 (2): 183-95, 1983.  [PUBMED Abstract]
   
   
6. Venkataramanan R, Ramachandran V, Komoroski BJ, et al.: Milk thistle, a herbal supplement, decreases the activity of CYP3A4 and uridine diphosphoglucuronosyl transferase in human hepatocyte cultures. Drug Metab Dispos 28 (11): 1270-3, 2000.  [PUBMED Abstract]
   
   
7. Zuber R, Modrianský M, Dvorák Z, et al.: Effect of silybin and its congeners on human liver microsomal cytochrome P450 activities. Phytother Res 16 (7): 632-8, 2002.  [PUBMED Abstract]
   
   
8. Hu Z, Yang X, Ho PC, et al.: Herb-drug interactions: a literature review. Drugs 65 (9): 1239-82, 2005.  [PUBMED Abstract]
   
   

Overall Level of Evidence for Milk Thistle

To assist readers in evaluating the results of human studies of complementary and alternative medicine (CAM) treatments for cancer, the strength of the evidence (i.e., the levels of evidence) associated with each type of treatment is provided whenever possible. To qualify for a level of evidence analysis, a study must:

• Be published in a peer-reviewed scientific journal.
• Report on therapeutic outcome or outcomes, such as tumor response, improvement in survival, or measured improvement in quality of life.
• Describe clinical findings in sufficient detail for a meaningful evaluation to be made.

Separate levels of evidence scores are assigned to qualifying human studies on the basis of statistical strength of the study design and scientific strength of the treatment outcomes (i.e., endpoints) measured. The resulting two scores are then combined to produce an overall score. A level of evidence score cannot be assigned to milk thistle because there has been insufficient clinical research to date. For an explanation of the scores and additional information about levels of evidence analysis of CAM treatments for cancer, refer to Levels of Evidence for Human Studies of Cancer Complementary and Alternative Medicine ².

Given the limited amount of human data, the use of milk thistle/silymarin as a treatment for cancer patients cannot be recommended outside the context of well-designed clinical trials.

Changes to This Summary (03/20/2008)

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

Editorial changes were made to this summary.

More Information

Additional Information about CAM Therapies

• The National Center for Complementary and Alternative Medicine ⁶ (NCCAM).
• The National Cancer Institute Office of Cancer Complementary and Alternative Medicine ⁷ (OCCAM).
• CAM on PubMed ⁸, a special subset of the PubMed scientific literature database created through a partnership between NCCAM and the National Library of Medicine.

About PDQ

• PDQ® - NCI's Comprehensive Cancer Database ⁹

  Full description of the NCI PDQ database.

Other PDQ Summaries

• PDQ® Cancer Information Summaries: Adult Treatment ¹⁰

  Treatment options for adult cancers.

• PDQ® Cancer Information Summaries: Pediatric Treatment ¹¹

  Treatment options for childhood cancers.

• PDQ® Cancer Information Summaries: Supportive and Palliative Care ¹²

  Side effects of cancer treatment, management of cancer-related complications and pain, and psychosocial concerns.

• PDQ® Cancer Information Summaries: Screening/Detection (Testing for Cancer) ¹³

  Tests or procedures that detect specific types of cancer.

• PDQ® Cancer Information Summaries: Prevention ¹⁴

  Risk factors and methods to increase chances of preventing specific types of cancer.

• PDQ® Cancer Information Summaries: Genetics ¹⁵

  Genetics of specific cancers and inherited cancer syndromes, and ethical, legal, and social concerns.

• PDQ® Cancer Information Summaries: Complementary and Alternative Medicine ¹⁶

  Information about complementary and alternative forms of treatment for patients with cancer.

Important:

This information is intended mainly for use by doctors and other health care professionals. If you have questions about this topic, you can ask your doctor, or call the Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).

Glossary Terms

4-NQO. A substance that is used in cancer research to cause tumors in laboratory animals. This is done to test new diets, drugs, and procedures for use in cancer prevention and treatment. Also called 4-NQO.

Cancer that begins in cells that line certain internal organs and that have gland-like (secretory) properties.

In cancer therapy, a drug or substance used in addition to the primary therapy.

Another treatment used together with the primary treatment. Its purpose is to assist the primary treatment. Also called adjunct therapy.

An unwanted side effect of treatment.

AAP. An enzyme that is used as a biomarker to detect damage to the kidneys, and that may be used to help diagnose certain kidney disorders. It is found at high levels in the urine when there are kidney problems. Also called AAP.

A type of poisonous mushroom that has harmful effects on the kidneys and liver. It is responsible for most fatal cases of mushroom poisoning. Also called death cap.

Blood vessel formation. Tumor angiogenesis is the growth of new blood vessels needed for tumors to grow. This is caused by the release of chemicals by the tumor.

An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models.

Having to do with reducing inflammation.

A substance that blocks the formation of neoplasms (growths that may become cancerous).

A substance that protects cells from the damage caused by free radicals (unstable molecules made by the process of oxidation during normal metabolism). Free radicals may play a part in cancer, heart disease, stroke, and other diseases of aging. Antioxidants include beta-carotene, lycopene, vitamins A, C, and E, and other natural and manufactured substances.

A substance that is used in cancer research to cause colon tumors in laboratory animals. This is done to test new diets, drugs, and procedures for use in cancer prevention and treatment.

A fluid made by the liver and stored in the gallbladder. Bile is excreted into the small intestine, where it helps digest fat.

A tube through which bile passes in and out of the liver.

Having to do with the liver, bile ducts, and/or gallbladder.

Substance formed when red blood cells are broken down. Bilirubin is part of the bile, which is made in the liver and is stored in the gallbladder. The abnormal buildup of bilirubin causes jaundice.

The ability of a drug or other substance to be absorbed and used by the body. Orally bioavailable means that a drug or other substance that is taken by mouth can be absorbed and used by the body.

The organ that stores urine.

A type of study in which the patients (single-blinded) or the patients and their doctors (double-blinded) do not know which drug or treatment is being given. The opposite of a blinded study is an open label study.

Having to do with, or derived from, plants.

Glandular organ located on the chest. The breast is made up of connective tissue, fat, and breast tissue that contains the glands that can make milk. Also called mammary gland.

Inflammation (swelling and reddening) of the bronchi.

An aggressive (fast-growing) type of B-cell non-Hodgkin lymphoma that occurs most often in children and young adults. The disease may affect the jaw, central nervous system, bowel, kidneys, ovaries, or other organs. There are three main types of Burkitt lymphoma (sporadic, endemic, and immunodeficiency related). Sporadic Burkitt lymphoma occurs throughout the world, and endemic Burkitt lymphoma occurs in Africa. Immunodeficiency-related Burkitt lymphoma is most often seen in AIDS patients.

A term for diseases in which abnormal cells divide without control. Cancer cells can invade nearby tissues and can spread to other parts of the body through the blood and lymph systems. There are several main types of cancer. Carcinoma is cancer that begins in the skin or in tissues that line or cover internal organs. Sarcoma is cancer that begins in bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue. Leukemia is cancer that starts in blood-forming tissue such as the bone marrow, and causes large numbers of abnormal blood cells to be produced and enter the blood. Lymphoma and multiple myeloma are cancers that begin in the cells of the immune system. Central nervous system cancers are cancers that begin in the tissues of the brain and spinal cord.

A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin).

The individual unit that makes up the tissues of the body. All living things are made up of one or more cells.

An increase in the number of cells as a result of cell growth and cell division.

The use of drugs, vitamins, or other agents to try to reduce the risk of, or delay the development or recurrence of, cancer.

The susceptibility of tumor cells to the cell-killing effects of anticancer drugs.

A drug used to treat cancer.

Treatment with drugs that kill cancer cells.

Any condition in which the release of bile from the liver is blocked. The blockage can occur in the liver (intrahepatic cholestasis) or in the bile ducts (extrahepatic cholestasis).

A disease or condition that persists or progresses over a long period of time.

A type of chronic, progressive liver disease in which liver cells are replaced by scar tissue.

A drug used to treat many types of cancer. Cisplatin contains the metal platinum. It kills cancer cells by damaging their DNA and stopping them from dividing. Cisplatin is a type of alkylating agent.

Having to do with the examination and treatment of patients.

A type of research study that tests how well new medical approaches work in people. These studies test new methods of screening, prevention, diagnosis, or treatment of a disease. Also called a clinical trial.

A type of research study that tests how well new medical approaches work in people. These studies test new methods of screening, prevention, diagnosis, or treatment of a disease. Also called a clinical study.

The longest part of the large intestine, which is a tube-like organ connected to the small intestine at one end and the anus at the other. The colon removes water and some nutrients and electrolytes from partially digested food. The remaining material, solid waste called stool, moves through the colon to the rectum and leaves the body through the anus.

CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices generally are not considered standard medical approaches. Standard treatments go through a long and careful research process to prove they are safe and effective, but less is known about most types of CAM. CAM may include dietary supplements, megadose vitamins, herbal preparations, special teas, acupuncture, massage therapy, magnet therapy, spiritual healing, and meditation. Also called CAM.

A clinical study that includes a comparison (control) group. The comparison group receives a placebo, another treatment, or no treatment at all.

A compound that is excreted from the body in urine. Creatinine levels are measured to monitor kidney function.

Cells of a single type (human, animal, or plant) that have been adapted to grow continuously in the laboratory and are used in research.

Cell-killing.

DNA. The molecules inside cells that carry genetic information and pass it from one generation to the next. Also called DNA.

A disease in which the body does not properly control the amount of sugar in the blood. As a result, the level of sugar in the blood is too high. This disease occurs when the body does not produce enough insulin or does not use it properly.

Frequent and watery bowel movements.

A product that is added to the diet. A dietary supplement is taken by mouth, and usually contains one or more dietary ingredient (such as vitamin, mineral, herb, amino acid, and enzyme). Also called nutritional supplement.

The amount of medicine taken, or radiation given, at one time.

Refers to the effects of treatment with a drug. If the effects change when the dose of the drug is changed, the effects are said to be dose-dependent.

A clinical trial in which neither the medical staff nor the person knows which of several possible therapies the person is receiving.

A drug that is used to treat many types of cancer and is being studied in the treatment of other types of cancer. Doxorubicin comes from the bacterium Streptomyces peucetius. It damages DNA (the molecules inside cells that carry genetic information) and stops cells from growing. Rapidly growing tumor cells that take up doxorubicin may die. It is a type of anthracycline antitumor antibiotic. Also called doxorubicin hydrochloride, Adriamycin PFS, Adriamycin RDF, and Rubex.

Upset stomach.

Having to do with the part of the cervix that protrudes into the vagina and is lined with epithelial cells.

Effectiveness. In medicine, the ability of an intervention (for example, a drug or surgery) to produce the desired beneficial effect.

In clinical trials, an event or outcome that can be measured objectively to determine whether the intervention being studied is beneficial. The endpoints of a clinical trial are usually included in the study objectives. Some examples of endpoints are survival, improvements in quality of life, relief of symptoms, and disappearance of the tumor.

A protein that speeds up chemical reactions in the body.

Refers to the cells that line the internal and external surfaces of the body.

A cell that carries oxygen to all parts of the body. Also called red blood cell and RBC.

A member of a group of substances found in many plants and plant-based foods. Flavonoids have shown antioxidant effects.

A highly reactive chemical that often contains oxygen and is produced when molecules are split to give products that have unpaired electrons (a process called oxidation). Free radicals can damage important cellular molecules such as DNA or lipids or other parts of the cell.

Solid material that forms in the gallbladder or common bile duct. Gallstones are made of cholesterol or other substances found in the gallbladder. They may occur as one large stone or as many small ones, and vary from the size of a golf ball to a grain of sand. Also called cholelith.

GI. Refers to the stomach and intestines. Also called GI.

A type of tumor that begins in the cells that give rise to sperm or eggs. Germ cell tumors can occur almost anywhere in the body and can be either benign or malignant.

The German Federal Institute for Drugs and Medical Devices Commission E. A committee made up of scientists, toxicologists, doctors, and pharmacists formed by the German government in 1978 to find out if herbs sold in Germany are safe and effective. The Commission has published information on the uses, side effects, and drug interactions of more than 300 herbs.

A substance found in plant and animal tissues that has many functions in a cell. These include activating certain enzymes and destroying toxic compounds and chemicals that contain oxygen.

A family of enzymes involved in metabolism and in making toxic compounds less harmful to the body.

A unit of weight in the metric system. One gram is equal to one thousandth of a kilogram and is approximately 30-times less than an ounce.

In medicine, loss of blood from damaged blood vessels. A hemorrhage may be internal or external, and usually involves a lot of bleeding in a short time.

Refers to the liver.

Disease of the liver causing inflammation. Symptoms include an enlarged liver, fever, nausea, vomiting, abdominal pain, and dark urine.

A type of adenocarcinoma, the most common type of liver tumor.

A liver tumor.

Enlarged liver.

An outdated term referring to non-Hodgkin lymphomas made up of large abnormal lymphoid cells. Histiocytic lymphomas include mature B-cell and T-cell non-Hodgkin lymphomas. Many tumors that were once called histiocytic lymphomas are now considered to be a type of large cell lymphoma.

The study of tissues and cells under a microscope.

An alternative approach to medicine based on the belief that natural substances, prepared in a special way and used most often in very small amounts, restore health. According to these beliefs, in order for a remedy to be effective, it must cause in a healthy person the same symptoms being treated in the patient. Also called homeopathy.

An anticancer drug that belongs to the family of drugs called alkylating agents.

In the laboratory (outside the body). The opposite of in vivo (in the body).

Redness, swelling, pain, and/or a feeling of heat in an area of the body. This is a protective reaction to injury, disease, or irritation of the tissues.

Having to do with inflammation (redness, swelling, pain, and a feeling of heat that helps protect tissues affected by injury or disease).

A hormone made by the islet cells of the pancreas. Insulin controls the amount of sugar in the blood by moving it into the cells, where it can be used by the body for energy.

Inside a cell.

Within the liver.

Into or within a vein. Intravenous usually refers to a way of giving a drug or other substance through a needle or tube inserted into a vein. Also called I.V.

In clinical trials, refers to a drug (including a new drug, dose, combination, or route of administration) or procedure that has undergone basic laboratory testing and received approval from the U.S. Food and Drug Administration (FDA) to be tested in human subjects. A drug or procedure may be approved by the FDA for use in one disease or condition, but be considered investigational in other diseases or conditions. Also called experimental.

A researcher in a clinical trial or clinical study.

One of two or more compounds that have the same chemical formula but different arrangements of the atoms within the molecules and that may have different physical/chemical properties.

A condition in which the skin and the whites of the eyes become yellow, urine darkens, and the color of stool becomes lighter than normal. Jaundice occurs when the liver is not working properly or when a bile duct is blocked.

One of a pair of organs in the abdomen. Kidneys remove waste from the blood (as urine), produce erythropoietin (a substance that stimulates red blood cell production), and play a role in blood pressure regulation.

A measure of weight. A kilogram is equal to 2.2 pounds.

Research done in a laboratory. These studies may use test tubes or animals to find out if a drug, procedure, or treatment is likely to be useful. Laboratory studies take place before any testing is done in humans.

A substance that promotes bowel movements.

Cancer that starts in blood-forming tissue such as the bone marrow and causes large numbers of blood cells to be produced and enter the bloodstream.

A ranking system used to describe the strength of the results measured in a clinical trial or research study. The design of the study (such as a case report for an individual patient or a randomized double-blinded controlled clinical trial) and the endpoints measured (such as survival or quality of life) affect the strength of the evidence.

Able to dissolve, be dissolved in, or absorb lipids (fats).

A large organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile.

A type of white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infections and other diseases.

In medicine, a mineral used by the body to help maintain muscles, nerves, and bones. It is also used in energy metabolism and protein synthesis.

Treatment that is given to help a primary (original) treatment keep working. Maintenance therapy is often given to help keep cancer in remission.

A byproduct of lipid (fat) metabolism in the body. It is also found in many foods and can be present in high amounts in rancid food.

A very thin layer of tissue that covers a surface.

A drug used to treat acute lymphatic leukemia. It belongs to the family of drugs called antimetabolites. Also called Purinethol.

Swelling of the abdomen caused by gas in the intestines or peritoneal cavity. Also called tympanites.

A drug used to treat some types of cancer, severe skin conditions such as psoriasis, and rheumatoid arthritis. Methotrexate stops cells from making DNA. It is a type of antimetabolite. Also called amethopterin and Rheumatrex.

A concentration of 1/1,000,000 (one millionth) molecular weight per liter (mol/L).

A plant that has been used in some cultures to treat certain medical problems, including stomach, liver, and gallbladder disorders. The active extract of milk thistle seeds is called silymarin. It is being studied in the prevention of liver damage caused by some cancer treatments. Also called Silybum marianum.

A measure of weight. A milligram is approximately 450,000 times smaller than a pound and 28,000 times smaller than an ounce.

A large number or variety.

A substance that is used in cancer research to cause bladder tumors in laboratory animals. This is done to test new diets, drugs, and procedures for use in cancer prevention and treatment.

Skin cancer that forms in basal cells or squamous cells but not in melanocytes (pigment-producing cells of the skin).

A clinical trial in which the participants are not assigned by chance to different treatment groups. Participants may choose which group they want to be in, or they may be assigned to the groups by the researchers.

Not harmful or destructive.

A type of study in which individuals are observed or certain outcomes are measured. No attempt is made to affect the outcome (for example, no treatment is given).

A type of study in which both the health providers and the patients are aware of the drug or treatment being given.

By or having to do with the mouth.

The concentration of particles dissolved in a fluid. The osmolality of serum can help diagnose several medical conditions such as dehydration, diabetes, and shock.

Having to do with the ovaries, the female reproductive glands in which the ova (eggs) are formed. The ovaries are located in the pelvis, one on each side of the uterus.

A condition in which antioxidant levels are lower than normal. Antioxidant levels are usually measured in blood plasma.

A term used to describe cancer that can be felt by touch, usually present in lymph nodes, skin, or other organs of the body such as the liver or colon.

PDQ is an online database developed and maintained by the National Cancer Institute. Designed to make the most current, credible, and accurate cancer information available to health professionals and the public, PDQ contains peer-reviewed summaries on cancer treatment, screening, prevention, genetics, complementary and alternative medicine, and supportive care; a registry of cancer clinical trials from around the world; and directories of physicians, professionals who provide genetics services, and organizations that provide cancer care. Most of this information, and more specific information about PDQ, can be found on the NCI's Web site at http://www.cancer.gov/cancertopics/pdq. Also called Physician Data Query.

Inflammation of the peritoneum (tissue that lines the abdominal wall and covers most of the organs in the abdomen). Peritonitis can result from infection, injury, or certain diseases. Symptoms may include swelling of the abdomen, severe pain, and weight loss.

A study to test whether a new treatment has an anticancer effect (for example, whether it shrinks a tumor or improves blood test results) and whether it works against a certain type of cancer.

The initial study examining a new method or treatment.

An inactive substance or treatment that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.

Refers to a clinical study in which the control patients receive a placebo.

The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma.

After death. Often used to describe an autopsy.

After a meal.

In medicine, the effect of increasing the potency or effectiveness of a drug or other treatment.

A substance that can produce oxygen byproducts of metabolism that can cause damage to cells.

An aggressive (fast-growing) type of acute myeloid leukemia in which there are too many immature blood-forming cells in the blood and bone marrow. It is usually marked by an exchange of parts of chromosomes 15 and 17. Also called acute promyelocytic leukemia and APL.

An attempt to prevent disease.

A gland in the male reproductive system. The prostate surrounds the part of the urethra (the tube that empties the bladder) just below the bladder, and produces a fluid that forms part of the semen.

The overall enjoyment of life. Many clinical trials assess the effects of cancer and its treatment on the quality of life. These studies measure aspects of an individual’s sense of well-being and ability to carry out various activities.

When referring to an experiment or clinical trial, the process by which animal or human subjects are assigned by chance to separate groups that compare different treatments or other interventions. Randomization gives each participant an equal chance of being assigned to any of the groups.

A tiny, round cluster of blood vessels within the kidneys. It filters the blood to reabsorb useful materials and remove waste as urine.

To make a copy or duplicate of something.

In medicine, an improvement related to treatment.

A problem that occurs when treatment affects healthy tissues or organs. Some common side effects of cancer treatment are fatigue, pain, nausea, vomiting, decreased blood cell counts, hair loss, and mouth sores.

A plant that has been used in some cultures to treat certain medical problems, including stomach, liver, and gallbladder disorders. The active extract of Silybum marianum seeds is called silymarin. It is being studied in the prevention of liver damage caused by some cancer treatments. Also called milk thistle.

A substance obtained from milk thistle seeds that is being studied in the prevention of liver damage caused by certain cancer treatments.

The part of the digestive tract that is located between the stomach and the large intestine.

An organ that is part of the lymphatic system. The spleen makes lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach.

Describes a mathematical measure of difference between groups. The difference is said to be statistically significant if it is greater than what might be expected to happen by chance alone. Also called significant.

Adding nutrients to the diet.

Having to do with treating disease and helping healing take place.

Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects.

A poison produced by certain animals, plants, or bacteria.

An abnormal mass of tissue that results when cells divide more than they should or do not die when they should. Tumors may be benign (not cancerous), or malignant (cancerous). Also called neoplasm.

Cells, tissues, or animals used to study the development and progression of cancer, and to test new treatments before they are given to humans. Animals with transplanted human tumors or other tissues are called xenograft models.

Invisible rays that are part of the energy that comes from the sun. UV radiation also comes from sun lamps and tanning beds. UV radiation can damage the skin and cause melanoma and other types of skin cancer. UV radiation that reaches the Earth's surface is made up of two types of rays, called UVA and UVB rays. UVB rays are more likely than UVA rays to cause sunburn, but UVA rays pass deeper into the skin. Scientists have long thought that UVB radiation can cause melanoma and other types of skin cancer. They now think that UVA radiation also may add to skin damage that can lead to skin cancer and cause premature aging. For this reason, skin specialists recommend that people use sunscreens that reflect, absorb, or scatter both kinds of UV radiation. Also called UV radiation.

Nitrogen in the blood that comes from urea (a substance formed by the breakdown of protein in the liver). The kidneys filter urea out of the blood and into the urine. A high level of urea nitrogen in the blood may be a sign of a kidney problem. Also called blood urea nitrogen and BUN.

Having to do with urine or the organs of the body that produce and get rid of urine.

A condition in which a vein, most often in the legs, becomes permanently enlarged, twisted, and painful. This may be caused by valves in the vein that don’t work properly or by weakness in the vein walls.

The active ingredient in a drug used to treat acute leukemia. It is used in combination with other drugs to treat Hodgkin disease, non-Hodgkin lymphoma, rhabdomyosarcoma, neuroblastoma, and Wilms tumor. Vincristine is also being studied in the treatment of other types of cancer. It blocks cell growth by stopping cell division. It is a type of vinca alkaloid and a type of antimitotic agent.