title: Inhibition of proliferation and expression of AR/PSA by herbal supplement Equiguard in LNCaP cells cultured in androgen-proficient FBS and androgen-deficient charcoal-stripped FBS is correlated with increased serine-15 phosphorylation of the tumor suppressor gene p53.
abstract: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, NY 10595, USA.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Lu
authors.forename: Junqiao
authors.initials: J
authors.lastname: Guo
authors.forename: Tze-Chen
authors.initials: TC
authors.lastname: Hsieh
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Wu
mesh_terms: D059002:Androgen Receptor Antagonists; D002606:Charcoal; D003470:Culture Media; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D008297:Male; D014411:Neoplastic Stem Cells / Q000187:drug effects; D010766:Phosphorylation; D008517:Phytotherapy / Q000379:methods*; D017430:Prostate-Specific Antigen / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D011944:Receptors, Androgen / Q000096:biosynthesis; D012694:Serine / Q000378:metabolism; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D059002:Androgen Receptor Antagonists; D003470:Culture Media; D004365:Drugs, Chinese Herbal; D006131:Growth Inhibitors; D011944:Receptors, Androgen; D016159:Tumor Suppressor Protein p53; D002606:Charcoal; D012694:Serine; D017430:Prostate-Specific Antigen