There has been increasing interest among patients, the media, and the medical community in the use of alternative and complementary therapies for the prevention and treatment of cancer. In particular, there has been growing interest in the use of dietary supplements such as selenium(Drug information on selenium) and vitamin E(Drug information on vitamin e), and herbal medications such as PC-SPES for the prevention and treatment of prostate cancer.
A recent cross-sectional survey of 357 patients at urology clinics and at a prostate cancer support group found that 27% to 39% of those with prostate cancer and 26% to 80% of those at high risk for prostate cancer used some form of complementary therapy. Vitamin E was the most popular such agent, used by 55% to 72% of patients taking complementary medicine. The average monthly cost of complementary therapy was $72 for patients surveyed at urology clinics and $33 for patients surveyed at a prostate cancer support group.
Similarly, a prospective study in 50 consecutive patients undergoing radiation therapy for prostate cancer found that 37% also used complementary therapies not prescribed by physicians. Herbal therapies were the most popular in this study, used by 60% of patients employing complementary therapies. In a separate survey of treating physicians, respondents believed that only 4% of their patients took part in complementary therapies. There appears to be widespread acceptance of complementary and alternative therapies among prostate cancer patients that often goes unrecognized and unreported by health-care practitioners.
This article will review the literature on commonly used herbal and dietary therapies for the prevention and treatment of prostate cancer.
Used by many prostate cancer patients, PC-SPES is an herbal combination that consists of eight extracts: Ganoderma lucidum, Panax pseudoginseng, Rabdosia rubescens, Chrysanthemum morifolium, Glycyrrhiza glabra (Spanish licorice), Isatis indigotica, Scutellaria baicalensis (skullcap), and Serenoa repens (saw palmetto).[3-5] This proprietary combination has been sold by Botanic Lab of Brea, California, since November 1996. Each capsule contains 320 mg of the herbal combination with an unknown ratio of each extract, and the cost of a monthly supply ranges from $162 to $486.
The components of PC-SPES may individually have some antineoplastic effects. For example, Ganoderma lucidum inhibits the development of sarcomas, Rabdosia rubescens inhibits the growth of sarcoma, hepatoma, cervical cancer, and lymphoma cells in vitro, and Scuttelaria baicalensis inhibits the growth of sarcoma and cervical cancer cell lines in vitro.[8-10] Panax pseudoginseng is thought to stimulate the activity of natural killer cells.
Saw palmetto, often used by patients as a separate supplement, inhibits the enzyme 5-alpha-reductase, which converts testosterone to its active form, dihydrotestosterone. The commonly used medication finasteride(Drug information on finasteride) (Proscar) also acts by inhibiting this enzyme. Like finasteride, saw palmetto has been shown to reduce symptoms among patients with benign prostatic hyperplasia.
Some components of PC-SPES may have estrogenic effects. For example, licorice has been shown to compete with estradiol(Drug information on estradiol) in an estrogen receptor-binding assay, and Isatis indigotica has been found to contain a phytoestrogen, beta-sitosterol.[4,12]
Recent studies have confirmed the hormonal activity of PC-SPES. DiPaola et al demonstrated that PC-SPES has estrogenic activity similar to that of estradiol. Diluted PC-SPES extract and estradiol also cause a dose-dependent increase in beta-galactosidase activity in a yeast reporter assay with the human estrogen receptor. In addition, diluted PC-SPES extract and estradiol both support the growth of an estrogen-dependent yeast strain.
PC-SPES can cause a significant increase in uterine weight in ovariectomized mice. Hsieh et al demonstrated that PC-SPES decreases the levels of secreted and intracellular prostate-specific antigen (PSA), as well as androgen-receptor expression in the prostate cancer cell line LNCaP. These in vitro studies and biologic assays indicate that PC-SPES has significant hormonal activity.
In Vitro Findings
Other studies have investigated the cytotoxic in vitro effects of PC-SPES. de la Taille et al reported that extracts of PC-SPES cause a dose-dependent reduction in cellular viability in the prostate cancer cell lines LNCaP, LNCaP-bcl-2, PC-3, and DU-145. The hormone-sensitive line LNCaP was affected by low doses of PC-SPES extract, whereas the hormone-insensitive lines LNCaP-bcl-2, PC-3, and DU-145 required higher doses for growth inhibition.
Further investigations have demonstrated that PC-SPES extracts can induce apoptosis in the hormone-sensitive cell line LNCaP, as well as in the hormone-insensitive cell lines PC3 and DU145. Moreover, Hsieh et al have shown that PC-SPES can induce apoptosis and down-regulate expression of the proto-oncogene bcl-6 in Mutu I cells. These results indicate that PC-SPES can be cytotoxic and induce apoptosis in vitro. There appear to be both hormonally mediated and hormone-independent pathways for the cytotoxic activity of PC-SPES.
In Vivo Findings
In vivo studies have also demonstrated the activity of PC-SPES. de la Taille et al implanted the hormone-insensitive prostate cancer cell line PC3 in immunodeficient nude mice. Mice treated with PC-SPES showed smaller tumors compared to untreated mice, although the difference was not statistically significant. Moreover, mice treated with PC-SPES had significantly lower weights of testis, prostate, bladder, and seminal vesicles compared to untreated mice.
Tiwari et al studied the effects of PC-SPES on inducible tumors in the Dunning R3327 rat prostate cancer cell model. Rats treated with dietary PC-SPES showed a dose-dependent inhibition of tumor incidence and rate of tumor growth. These animal studies suggest that PC-SPES may have hormonal effects and antineoplastic activity in vivo.