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The Role of PC-SPES, Selenium, and Vitamin E in Prostate Cancer

The Role of PC-SPES, Selenium, and Vitamin E in Prostate Cancer

ABSTRACT: Prostate cancer patients commonly use complementary and alternative medications. There has been growing interest in recent years in the role of the herbal medication PC-SPES and the essential nutrients selenium and vitamin E in the prevention and treatment of prostate cancer. This article reviews the preclinical and clinical studies of these therapies. It is critical that health-care professionals be aware of the potential role and side effects of these widely used complementary and alternative therapies. [ONCOLOGY 16:285-300, 2002]

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 and
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.[1] 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.[2] 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.[2] 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.

PC-SPES

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.[6] 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.[7]

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.[9]

Hormonal Activity

Saw palmetto, often used by patients as a separate supplement, inhibits the
enzyme 5-alpha-reductase, which converts testosterone to its active form,
dihydrotestosterone.[3] The commonly used medication finasteride (Proscar) also
acts by inhibiting this enzyme. Like finasteride, saw palmetto has been shown to
reduce symptoms among patients with benign prostatic hyperplasia.[11]

Some components of PC-SPES may have estrogenic effects. For example, licorice
has been shown to compete with 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.[3] 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.[13] These in vitro studies
and biologic assays indicate that PC-SPES has significant hormonal activity.

Cytotoxic Effects

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.[14] 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.[4] 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.[15] 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.[4] 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.[16] 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.

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