In vitro studies using a variety of human cell lines have been used to assess the effectiveness of antineoplastons as antineoplastic agents. Burzynski states that antineoplaston A is species-specific because it had no therapeutic effect when the human preparation was tested on animal tumor systems. Although this finding limits the usefulness of animal model testing, the developer has suggested that a “marked” therapeutic effect was produced in a xenograft bearing human tumor tissue.[1] This claim is made only for antineoplaston A. Other formulations of antineoplastons have not been tested in animal models.

Japanese scientists have tested antineoplastons A10 and AS2-1 in vitro for cell growth inhibition and progression in several human hepatocellular cell lines.[2,3] Tests were performed in a dose-dependent manner at concentrations varying from 0.5 to 8 µg/mL for A10 and AS2-1, and growth inhibition was generally observed at 6 to 8 µg/mL. This dose level is considered excessively high and generally reflects a lack of activity. Growth inhibition of one of the cell lines (KIM-1) was observed at low concentration for a mixture of cisplatin (CDDP) and A10, but this result was probably caused by the cisplatin, which was effective at concentrations of 0.5 to 2.0 μg/mL when tested alone.[4] AS2-1 was reported to induce apoptosis in three of the cell lines at concentrations of 2 and 4 μg/mL.

Antineoplaston A10 was also shown to inhibit prolactin or interleukin-2 stimulation of mitogenesis in a dose-dependent manner in rat Nb2 lymphoma cell line. The addition of A10 (1–12 mm) to prolactin-stimulated cells inhibited growth but was reversible when A10 was removed, suggesting a cytostatic rather than cytotoxic mechanism of action. A10 also showed no toxicity in a chromium release assay. DNA synthesis was also inhibited by A10.[5]

The ability of antineoplaston A3, isolated from urine and not an analog, to inhibit the growth of the HBL-100 human breast cancer cell line in vitro was investigated in a study that also examined the toxicity of A3 in Swiss white mice. Antineoplaston A3 inhibited colony formation in a dose-dependent manner over a dose range of 0.05, 0.1, 0.2, and 0.4 µg/mL.[6]

A somewhat different approach to the use of A10 was taken by researchers in Egypt. Taking the developer’s initial ideas about the presence of A10 in the urine of patients, this study looked for the amount of A10 in the urine of 31 breast cancer patients and compared this to the amount in 17 healthy controls. They found significantly (P < .001) less A10 in the urine of breast cancer patients than in controls, suggesting that the amount of A10 in urine has a potential use as a screening tool.[7]

The same researchers looked at the immunomodulating potential of A10 by examining the inhibition of neutrophil apoptosis induced by A10 in vitro. Neutrophils from 28 breast cancer patients and 28 controls were obtained from blood samples. Urine samples were obtained from the same patients and tested for the presence of A10. Cancer patients had significantly (P < .001) higher levels of neutrophil apoptosis and significantly lower levels of A10. Neutrophil apoptosis was assessed by adding A10 at a dose of 10 µg/mL to the cellular suspensions of 42 breast cancer patients. Nontreated samples were used as controls. A10 was found to significantly inhibit neutrophil apoptosis (P < .0001).[8]

Several analogs of antineoplaston A10 have been synthesized and their antineoplastic activity tested against various cell lines. These include aniline mustard analogs of antineoplaston A10 and Mannich bases of antineoplaston A10.[9,10] These analogs showed improved in vitro antitumor activity over that of antineoplaston A10.

References

1. Burzynski SR, Stolzmann Z, Szopa B, et al.: Antineoplaston A in cancer therapy. (I). Physiol Chem Phys 9 (6): 485-500, 1977.  [PUBMED Abstract]
   
   
2. Tsuda H: Inhibitory effect of antineoplaston A-10 on breast cancer transplanted to athymic mice and human hepatocellular carcinoma cell lines. The members of Antineoplaston Study Group. Kurume Med J 37 (2): 97-104, 1990.  [PUBMED Abstract]
   
   
3. Tsuda H, Iemura A, Sata M, et al.: Inhibitory effect of antineoplaston A10 and AS2-1 on human hepatocellular carcinoma. Kurume Med J 43 (2): 137-47, 1996.  [PUBMED Abstract]
   
   
4. Tsuda H, Sugihara S, Nishida H, et al.: The inhibitory effect of the combination of antineoplaston A-10 injection with a small dose of cis-diamminedichloroplatinum on cell and tumor growth of human hepatocellular carcinoma. Jpn J Cancer Res 83 (5): 527-31, 1992.  [PUBMED Abstract]
   
   
5. Wood JC, Copland JA, Muldoon TG, et al.: 3-phenylacetylamino-2,6-piperidinedione inhibition of rat Nb2 lymphoma cell mitogenesis. Proc Soc Exp Biol Med 197 (4): 404-8, 1991.  [PUBMED Abstract]
   
   
6. Lee SS, Mohabbat MO, Burzynski SR: In vitro cancer growth inhibition and animal toxicity studies of antineoplaston A3. Drugs Exp Clin Res 13 (Suppl 1): 13-6, 1987.  [PUBMED Abstract]
   
   
7. Badria F, Mabed M, Khafagy W, et al.: Potential utility of antineoplaston A-10 levels in breast cancer. Cancer Lett 155 (1): 67-70, 2000.  [PUBMED Abstract]
   
   
8. Badria F, Mabed M, El-Awadi M, et al.: Immune modulatory potentials of antineoplaston A-10 in breast cancer patients. Cancer Lett 157 (1): 57-63, 2000.  [PUBMED Abstract]
   
   
9. Choi BG, Kim OY, Chung BH, et al.: Synthesis of antineoplaston A10 analogs as potential antitumor agents. Arch Pharm Res 21 (2): 157-63, 1998.  [PUBMED Abstract]
   
   
10. Hendry LB, Chu CK, Copland JA, et al.: Antiestrogenic piperidinediones designed prospectively using computer graphics and energy calculations of DNA-ligand complexes. J Steroid Biochem Mol Biol 48 (5-6): 495-505, 1994.  [PUBMED Abstract]
    
    

Glossary Terms

In chemistry, a substance that is similar, but not identical, to another.

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.

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

A substance isolated from normal human blood and urine that is being tested as a type of treatment for some tumors and AIDS.

Having to do with stopping abnormal cell growth.

A type of cell death in which a series of molecular steps in a cell leads to its death. This is the body’s normal way of getting rid of unneeded or abnormal cells. The process of apoptosis may be blocked in cancer cells. Also called programmed cell death.

A laboratory test to find and measure the amount of a specific substance.

A tissue with red blood cells, white blood cells, platelets, and other substances suspended in fluid called plasma. Blood takes oxygen and nutrients to the tissues, and carries away wastes.

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.

Cancer that forms in tissues of the breast, usually the ducts (tubes that carry milk to the nipple) and lobules (glands that make milk). It occurs in both men and women, although male breast cancer is rare.

A term for diseases in which abnormal cells divide without control and can invade nearby tissues. Cancer cells can also 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.

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

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.

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.

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

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.

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

One of a group of related proteins made by leukocytes (white blood cells) and other cells in the body. Interleukin-2 is made by a type of T lymphocyte. It increases the growth and activity of other T lymphocytes and B lymphocytes, and affects the development of the immune system. Aldesleukin (interleukin-2 made in the laboratory) is being used as a biological response modifier to boost the immune system in cancer therapy. Interleukin-2 is a type of cytokine. Also called IL-2.

Cancer that begins in cells of the immune system. There are two basic categories of lymphomas. One kind is Hodgkin lymphoma, which is marked by the presence of a type of cell called the Reed-Sternberg cell. The other category is non-Hodgkin lymphomas, which includes a large, diverse group of cancers of immune system cells. Non-Hodgkin lymphomas can be further divided into cancers that have an indolent (slow-growing) course and those that have an aggressive (fast-growing) course. These subtypes behave and respond to treatment differently. Both Hodgkin and non-Hodgkin lymphomas can occur in children and adults, and prognosis and treatment depend on the stage and the type of cancer.

A type of immune cell that is one of the first cell types to travel to the site of an infection. Neutrophils help fight infection by ingesting microorganisms and releasing enzymes that kill the microorganisms. A neutrophil is a type of white blood cell, a type of granulocyte, and a type of phagocyte.

Closely monitoring a patient's condition but withholding treatment until symptoms appear or change. Also called active surveillance, expectant management, and watchful waiting.

In medicine, the course of a disease, such as cancer, as it becomes worse or spreads in the body.

A hormone that is made by the pituitary gland (a pea-sized organ in the center of the brain). Prolactin causes a woman’s breasts to make milk during and after pregnancy, and has many other effects in the body.

Checking for disease when there are no symptoms. Since screening may find diseases at an early stage, there may be a better chance of curing the disease. Examples of cancer screening tests are the mammogram (breast), colonoscopy (colon), Pap smear (cervix), and PSA blood level and digital rectal exam (prostate). Screening can also include checking for a person’s risk of developing an inherited disease by doing a genetic test.

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

A group or layer of cells that work together to perform a specific function.

The extent to which something is poisonous or harmful.

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 cancer), or malignant (cancer). Also called neoplasm.

Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra.

The cells of one species transplanted to another species.