- How It Works
- Purported Uses
- Research Evidence
- Patient Warnings
- Do Not Take If
- Side Effects
- Dosage (Inside MSKCC Only)
Common Name
Genistein Combined Polysaccharide
Brand Name
GCPTM
Clinical Summary
A nutritional supplement prepared by fermenting soy extract with basidiomycetes. Genistein Combined Polysaccharide (GCP) is composed of two ingredients, genistein, a soy isoflavone, and polysaccharides obtained from a variety of mushrooms. Isoflavones have been shown to influence hormone-dependent cancers due to their estrogenic behavior. Basidiomycetes express immune-stimulant (1) and antitumor (2) (3) activity in vitro. In prostate cancer cells, GCP was found to reduce androgen receptor and prostate specific antigen levels, induce cell growth arrest, and modestly increase apoptosis (4). GCP was also found to inhibit cell growth and induce apoptosis in androgen-dependent and -independent human prostate cancer cell lines (5). It was also found to potentiate the cytostatic and cytotoxic activities of docetaxel, bicalutamide, and the sRC kinase inhibitor, pp2 (5). Another study in three human lymphoid cell ines found that GCP treatment resulted in significant inhibition of cell proliferation and arrested the cell cycle in the G2/M phase (6). One case report shows full regression of T3 prostate cancer after six weeks of treatment with GCP (7). However, no large scale clinical trials have been performed to verify GCP’s potential anticancer properties.
Purported Uses
- Cancer prevention
- Prostate cancer
Constituents
- Genistein
- Basidiomycetes polysaccharides
Mechanism of Action
In vitro experiments show that genistein inhibits tyrosine-specific protein kinase activity of EGF receptors. Inhibition is competitive with respect to ATP and noncompetitive to a phosphate acceptor, histone H2B. Genistein bears no structural relationship with ATP, so inhibition may not be due to true competition for the same active site as that utilized by ATP (8). Basidiomycetes polysaccharides have been shown to possess antitumor, antiviral, antibacterial and immune-modulating activities. The fermentation of soy extract with basidiomycetes deglycosylates the soy isoflavones which renders them in a highly absorbable form (7). In prostate cancer cells, GCP was found to inhibit mammalian target of rapamycin (MTOR) activity (4). MTOR is a downstream effector of Akt, an enzyme which plays an important role in cancer cell proliferation and survival (4). (For more information on the mechanism of genistein action, see soy monograph.)
Pharmacokinetics
Absorption
Natural isoflavones are glycosylated and poorly absorbed. Fermentation of soy extract deglycosylates the isoflavones which are absorbed more readily.
(7)
Herb-Drug Interactions
Tamoxifen: Animal studies suggest that genistein, a soy isoflavone, may antagonize the effects of tamoxifen on estrogen-dependent breast cancer.
(9)
Literature Summary and Critique
Ghafar MA, et al. Regression of prostate cancer following administration of Genistein Combined Polysaccharide (GCP), a nutritional supplement: a case report. J Altern Complement Med 2002;8:493-7.
A 63-year-old man presenting with T3, Gleason grade 6 (3+3) acinar type invasive localized adenocarcinoma of the right prostatic lobe experienced full regression after six weeks of treatment with 1.5 g/day oral GCP. Cancer was diagnosed by clinical examination, ultrasound, prostate, and seminal vesicle biopsy. Radical prostatectomy was performed after GCP treatment at which point absence of residual invasive adenocarcinoma was confirmed. Only a prostate intraepithelial neoplasia was identified. PSA levels dropped from 19.4 to 4.0 ng/ml in the 44 days of treatment and decreased to undetectable levels after prostatectomy. No side effects were reported. The case study supports GCP as an option in advanced prostate cancer patients who have failed other forms of conventional therapy, but further studies need to be performed.
References
- Rice L, et al. Mechanisms of the growth inhibitory effects of the isoflavonoid biochanin A on LNCaP cells and xenografts. Prostate 2002;52:201-12.
- Mentor-Marcel R, et al. Genistein in the diet reduces the incidence of poorly differentiated prostatic adenocarcinoma in transgenic mice (TRAMP). Cancer Res 2001;61:6777-82.
- Yuan L, Wagatsuma C, Sun B, Kim JH, Surh YJ. The role of beta-glucuronidase in induction of apoptosis by genistein combined polysaccharide (GCP) in xenogeneic mice bearing human mammary cancer cells. Ann N Y Acad Sci. 2003 Dec;1010:347-9.
- Vinall RL, Hwa K, Ghosh P, Pan CX, Lara PN Jr, de Vere White RW. Combination treatment of prostate cancer cell lines with bioactive soy isoflavones and perifosine causes increased growth arrest and/or apoptosis. Clin Cancer Res. 2007 Oct 15;13(20):6204-16.
- Burich RA, Holland WS, Vinall RL, et al. Genistein combined polysaccharide enhances activity of docetaxel, bicalutamide and Src kinase inhibition in androgen-dependent and independent prostate cancer cell lines. BJU Int. 2008 Nov;102(10):1458-66.
- McCall JL, Burich RA, Mack PC. GCP, a genistein-rich compound, inhibits proliferation and induces apoptosis in lymphoma cell lines. Leuk Res. 2010. Jan;34(1):69-76.
- Ghafar MA, et al. Regression of prostate cancer following administration of Genistein Combined Polysaccharide (GCP), a nutritional supplement: a case report. J Altern Complement Med 2002;8:493-7.
- Akiyama T, et al. Genistein, a specific inhibitor of tyrosine-specific protein kinases. J Biol Chem 1987;262:5592-5.
- Ju YH, et al. Dietary genistein negates the inhibitory effects of tamoxifen on growth of estrogen-dependent human breast cancer (MCF-7) cells implanted in athymic mice. Can Res 2002;62:2474-7.
How It Works
Bottom Line: There is no proof that GCP can prevent or treat cancer in humans. Although the ingredients in GCP show anti-cancer activity in the laboratory, it is not known how they interact with each other or if they have any effect in the human body.
Genistein Combined Polysaccharide (GCP) is composed of genistein, a soy isoflavone, and polysaccharides derived from Basidiomycetes mushrooms. Although GCP itself has not been studied in the laboratory, genistein and Basidiomycetes mushrooms have, with the following results.
Genistein has been studied extensively in laboratory experiments. These generally show that genistein, when directly applied to several types of cancer cells (including ER+ and ER- breast cancer, prostate cancer, neuroblastoma and sarcoma), inhibits their growth and replication. Genistein 1) competes with the body’s own estrogen and 2) inhibits the ability of a growth factor called EGF to stimulate its receptor and cause downstream cellular effects. Estrogen and EGF can enhance the growth of certain tumors (such as ER+ breast cancer), so scientists think that genistein might act against them to slow tumor growth. This theory has not been confirmed in humans through clinical studies, however.
Laboratory research has suggested that the polysaccharides in Basidiomycetes mushrooms can slow the growth of tumors, enhance certain activities of immune cells, and kill some bacteria and viruses on contact. It is not clear to what extent these effects occur in the human body.
Purported Uses
- To prevent and treat cancer
Genistein shows anti-tumor activity in the laboratory setting, but the same has not been shown for GCP, and there is no proof from clinical trials that GCP can prevent or treat cancer in humans. - To treat prostate cancer
One case report weakly supports this use, but there is no proof from clinical trials to support this finding.
Research Evidence
No clinical trials have tested the effectiveness of GCP for any of its proposed uses.
Prostate cancer:
One case report described the use of GCP by a 63-year-old man with invasive adenocarcinoma of the prostate. After six weeks of treatment with 1.5 grams of GCP by mouth daily, the man experienced a full regression (shrinking) of his tumor. Surgery to fully remove the prostate was performed after the treatment with GCP, and the surgeons found that the tumor was no longer invading the surrounding tissue. The patient’s PSA levels dropped significantly during GCP treatment and decreased to undetectable levels after his surgery. However, the problem with case reports is that they recount the effect of a drug or supplement on only one individual, and there always remains the possibility that the effects were due to another variable in the patient’s life, or to pure chance. The effectiveness of GCP would have to be observed in numerous patients in order for its use to considered valid.
Patient Warnings
- It is still controversial whether patients with estrogen-dependent tumors should take soy products such as genistein, due to its possible estrogenic activity. Patients should ask their doctors.
Do Not Take If
- You are undergoing chemotherapy with tamoxifen (Studies in animals suggest that genistein may lessen its effects).
Side Effects
None known
Dosage (Inside MSKCC Only)
This field is only visible to only Inside MSKCC users.
Aliases
Genistein Combined Polysaccharide
Last updated: March 4, 2011
E-mail your questions and comments to aboutherbs@mskcc.org.
