Use of dietary supplements and botanical products is widely accepted by patients diagnosed with
prostate cancer (CaP) as a primary or complementary form of treatment for their medical conditions in the U.S. Yet, the majority of these products have not been rigorously studied with regard to scientific mechanism(s). Because many of the available products are mixtures of multiple extracts derived from plants, some of which are not necessarily native to the U.S., we consider mechanistic studies under defined laboratory conditions to be valuable and essential, not only from the standpoint of standardization and possible contamination with the products, but also in providing insights and scientific evidence for the clinical efficacy some of these products purportedly demonstrate. In previous studies from this laboratory,
Equiguard, a composite supplement consisting of standardized extracts from nine Chinese herbs, which was originally formulated to correct physiological decline in kidney functions associated with age, was fortuitously found to display anti-CaP properties. Using a panel of CaP cells, we showed that
ethanol extracts of
Equiguard significantly inhibited
cancer cell growth, induced apoptosis, lowered expression of the
androgen receptor (AR), decreased intracellular and secreted
prostate-specific antigen (PSA) levels and completely abolished the colony forming activities of CaP cells. Since responsiveness to
Equiguard was observed in cells mimicking the
androgen-dependent (AD) and
androgen-independent (AI) states of CaP, our results raise the interesting possibility that this herbal supplement may potentially prevent, delay or circumvent the onset of AI, and thereby induce chronic instead of terminal CaP. Since
androgen ablation
therapy (chemical or surgical
castration) is the mainstay for localized CaP, we questioned whether
Equiguard might still exert the aforementioned activities in experimental settings modeled after
androgen ablation. Accordingly, we studied the effects of
Equiguard in LNCaP cells, cultured in
androgen-proficient (FBS) or -deficient (CS-FBS) media that simulate the hormonal status pre- and post-
castration in vivo. Extracts of
Equiguard were effective in reducing colony formation, proliferation and
PCNA expression of cells cultured in CS-FBS. Moreover, within a concentration range of
Equiguard, the prostate-specific genes, PSA and AR, were affected to a similar extent in cells cultured either in FBS or CS-FBS, and were correlated with increased phosphorylation at serine-15 of the tumor suppressor gene p53. These results are consistent with the interpretation that the anti-proliferative and gene modulatory properties of
Equiguard are largely independent of the status of
androgens in the
culture media.