Note: A separate PDQ summary on Prostate Cancer Treatment is also available.

PC-SPES is a patented herbal mixture that was sold as a dietary supplement and used as a complementary and alternative medicine (CAM) treatment for prostate cancer. It is a combination of eight herbs: baikal skullcap (Scutellaria baicalensis Georgi), chrysanthemum (Dendranthema morifolium [Ramat.] Tzvelev [synonym Chrysanthemum morifolium]), ganoderma (Ganoderma lucidum [Curtis:fr] Karst.), isatis (Isatis indigotica Fort.), licorice (Glycyrrhiza glabra L. or Glycyrrhiza uralensis Fisch. ex DC.), Panax ginseng C.A. Meyer or pseudo ginseng (Panax pseudoginseng var. notoginseng Hoo & tseng [synonym Panax notoginseng (Burkill)] F.H.Chen), Isodon rubescens (Hemsl.) Hara (synonym Rabdosia rubescens [Hemsl.] Hara), and saw palmetto (Serenoa repens [Bartr.] Small). With the exception of saw palmetto, the herbs in PC-SPES have been used individually or in combination in Traditional Chinese Medicine (TCM) for a variety of health problems, including those of the prostate, for hundreds of years.[1,2]

PC-SPES is an herbal product that resulted from a collaboration between a chemist at the New York Medical College in Valhalla, New York, and a Chinese herbalist and doctor of TCM in China. Their idea was to combine TCM with the scientific techniques of Western laboratory research. In the United States, a series of in vitro and in vivo laboratory studies was started on the mixture of herbs used in TCM specially formulated to treat prostate problems. Researchers published the results of these studies, which showed promising anticancer activity from PC-SPES.[3-11]

In 1997, the herbal formula for PC-SPES was patented in the United States.[12] A company, BotanicLab (Brea, California), was formed to produce, distribute, and sell the product. PC-SPES was sold through the BotanicLab Web site (the Web site was taken down after PC-SPES was recalled) and through selected distributors. Anecdotal information about the product and its positive effects was widely circulated on the Internet through Web sites that informed prostate cancer patients about new developments in treatment. At the same time, the published papers were being read by the scientific community, and the findings were presented at various conferences. As a result, clinicians and researchers began looking at PC-SPES as one of the first viable treatments to come out of the alternative medicine community.

The manufacturing process for PC-SPES has been described by the manufacturer as follows: extracts of raw plant material were obtained from the specified plants, which were grown in particular geographic regions in China and harvested at certain times of the year to reduce the natural variation inherent in any biological product. The extracts were shipped to the United States, where high-performance liquid chromatography (HPLC) was used to monitor the key active compounds—which are believed to be directly related to the clinical effects—for batch-to-batch reproducibility. Activity-related biomarkers were kept in a constant concentration from lot to lot. A commercial testing laboratory (Truesdail Laboratory, Tustin, California) was used to guarantee that each batch was free from contamination with heavy metals, pesticides, microorganisms and products, and prescription drugs. Each lot was standardized by an anticancer bioassay for an effective dose of 50% in vitro inhibition of cell growth using human LNCaP cells for androgen-dependent (AD) prostate cancer and DU-145 cells for androgen-independent (AI) prostate cancer. The powder was then encapsulated, bottled, labeled, and sterilized at the BotanicLab facility.[10]

In 2001, allegations that PC-SPES contained the synthetic estrogen diethylstilbestrol (DES) started to appear on e-mail listservs used by prostate cancer patients and in online newsletters. Prostate cancer patients who were taking PC-SPES noticed that their recent medication was not as effective as the previous batches.[13] A sample of PC-SPES submitted to a testing laboratory by BotanicLab in August 2001 found no DES. BotanicLab posted the letter from the laboratory on their Web site, claiming that PC-SPES contained no DES. However, in other tests of six different lots of PC-SPES received from two different sources in August 2001, Rocky Mountain Instrumental Laboratory found varying amounts of DES in three lots. More tests done for the California Department of Health Services in February 2002 did not find DES but did find warfarin, a prescription drug used as a blood thinner.[14]

The presence of a synthetic estrogen such as DES was suspected early in the clinical use of PC-SPES after reports in the literature discussed the mixture’s estrogen-like ability to lower prostate-specific antigen (PSA) levels in AD prostate cancer patients. In addition, the side effects of treatment were similar to those of estrogen therapy. [15-17] In one study, patients who showed the most response to PC-SPES were also those who were the most responsive to DES. Reviewed in [11,18] The same study also attempted to find out whether DES or similar compounds were present in PC-SPES. Transcriptional activation assays in yeast strain PL3 Saccharomyces cerevisiae using an ethanolic extract of PC-SPES showed estrogenic activity similar to 1nM estradiol. In addition, ovariectomized CD-1 mice showed substantially increased uterine weights. HPLC, gas chromatography, and mass spectrometry did not reveal the presence of DES but rather that of a compound with similar chemical characteristics. The authors of the report concluded that PC-SPES contains estrogenic compounds that are distinct from DES or other synthetic estrogens.[18]

A definitive evaluation of PC-SPES analyzed specific lots of PC-SPES capsules manufactured from 1996 to 2001.[19] In addition to using HPLC to isolate, identify, and quantify the synthetic drugs and active phytoestrogens, this study also identified components using proton nuclear magnetic resonance, gas chromatography/mass spectrometry, and mass spectra analysis. Tests showed the presence of the synthetic drugs indomethacin (a nonsteroidal anti-inflammatory drug not previously reported in the literature or found in other testing), DES, and warfarin. Testing was also done for concentrations of the two naturally occurring phytosterols, licochalcone A and baicalin. Test results indicated a history of rising and falling levels of contamination by the three synthetic drugs and a recent rise in the naturally occurring phytochemicals in PC-SPES. Lots of PC-SPES manufactured in 1996 through mid-1999 contained indomethacin ranging from 1.07 to 13.19 mg/g and DES ranging from 107.28 to 159.27 µg/g and were 2 to 6 times more antineoplastic and up to 50 times more estrogenic than lots manufactured after the spring of 1999. In vitro testing of ethanolic extracts of PC-SPES against LNCaP, PC-3, and DU-145 prostate cancer cell lines showed a decrease in both antineoplasticity and estrogenicity in lots of PC-SPES manufactured in June 1998 through August 2001, which correlated with the amount of DES and indomethacin contamination.[19] Another in vitro test of suspected lots of PC-SPES manufactured from 2000 to 2001 also showed the presence of DES.[20] The table below shows the lot numbers, date of manufacture, and amount of DES contamination.

Refer to chart 1 below showing the lot numbers, date of manufacture, and amount of DES contamination.

Although the laboratory testing showed that certain lots of the mixture contained indomethacin, warfarin, and DES, the amount of DES present may not have accounted for all of the estrogenic effect of PC-SPES. There is some evidence that the mixture acts differently from DES at the molecular level.[7,21] In addition, its anticancer effects on both AI prostate cancer and AD prostate cancer may point to a mechanism other than estrogen-like activity.[19,22,23] The in vitro activity of PC-SPES against cancer cells other than prostate also gives rise to the speculation that its estrogen-like qualities might not account for all of the mixture’s anticancer activity.[24,25]

Considerable research has been conducted on the anticancer properties of the eight individual botanicals in PC-SPES.

Baikal skullcap (Scutellaria baicalensis)—Chinese name huang qin—contains baicalin and wogonin, two active flavones. Baicalin converts to baicalein, which is another active flavone. In vitro, baicalin and baicalein inhibit cell growth of AD LNCaP and JCA-1 AI human prostate cancer cell lines [24,25], as well as inducing apoptosis in human LNCaP cells.[26] Baicalin also shows antimutagenic and antioxidant activity in vitro as well as free radical scavenging ability.[27-32]

Licorice (Glycyrrhiza glabra or Glycyrrhiza uralensis)—Chinese name gan cao—contains the very active flavonoid licochalcone A, which has demonstrated in vitro estrogenic activity.[33] This botanical shows a broad range of anticancer activity in vitro. It enhances the cytotoxicity of commonly used anticancer drugs and induces apoptosis in MCF-7 human breast cancer and HL-60 promyelocytic leukemia cell lines.[33-36]

Reishi mushroom (Ganoderma lucidum [Curtis: fr.] Karst.)—Chinese name ling zhi— has been shown to aid in the recovery of leukocyte counts in irradiated mice in a dose-dependent manner. It contains the polysaccharide G009, which has demonstrated antioxidant behavior against HL-60 cells in vitro and dose-dependent inhibition of lipid peroxidation in rat brain cells in vitro.[37-41]

Isatis (Isatis indigotica)—Chinese name da qing ve—contains active agents in each part of the plant.[2] TCM has different names for the medicinals coming from the leaf, stem, and root and uses these plant products for different purposes. Indirubin, an active ingredient, and its analogs have demonstrated inhibition of cyclin-dependent kinases in human mammary carcinoma cell line MCF-7 in vitro.[42]

Ginseng (Panax ginseng or Panax pseudoginseng var. notoginseng)— Chinese name tianqi—contains ginsenosides and saponins. Of the 30 ginsenosides that have been isolated from Panax ginseng, only the 20(S)-protopanaxadiol type R3 has inhibited cell growth and suppressed PSA expression, androgen receptor and 5-alpha-reductase activity, and PCNA production in vitro.[43-45]

Chrysanthemum flowers (Dendranthema morifolium)—Chinese name ju hua—contain triterpene diols and triols. Arnidiol exhibited cytotoxicity in vitro against 58 of the 60 human cancer cell lines developed by the National Cancer Institute (NCI) Developmental Therapeutics Program.[46]

The botanical rabdosia rubescens (Isodon rubescens)—Chinese name dong ling cao—has two very active agents, oridonin and rubesencin b. Oridonin inhibits DNA synthesis in vitro Reviewed in [1], and rubesencin b inhibited cell growth in cancer cell lines in vitro and in a mouse model.[47]

Saw palmetto (Serenoa repens) is the only botanical in PC-SPES that is not used in TCM. There is strong evidence from human trials that saw palmetto has some activity against benign prostatic hypertrophy (BPH), including improved urine flow and less erectile dysfunction when compared with placebo or finasteride. S repens also exhibits antiestrogenic activity in placebo-controlled BPH trials. In LNCaP cells, S repens produced apoptosis in vitro.[48-52]

Exactly how PC-SPES works in the body is still unknown. The presence of contaminants and varying amounts of the active agents in each lot of PC-SPES complicate the interpretation of any results from studies that might lead to an explanation of its mechanisms of action. More studies of the individual components of the mixture and testing of a standard formulation that is free of contaminants are needed before any conclusions can be reached about the level of cytotoxicity, antineoplasticity, or estrogenicity of PC-SPES.

The National Center for Complementary and Alternative Medicine (NCCAM) stopped funding to studies of PC-SPES after the drug contamination was detected and made public, although the laboratory studies were later resumed. Refer to The Future of PC SPES Research Funding by NCCAM.

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