The Chinese herbal preparation designated PC-SPES, which is comprised of a mixture of the extracts of eight different herbs, is gaining increasing acceptance as a complimentary or alternative treatment for prostate cancer because of its ability to arrest tumor growth. The overall goal of this proposal is to understand the mechanism(s) by which PC-SPES acts to inhibit prostate cell growth. Our preliminary study in rats, demonstrated that PC-SPES could significantly reduce prostate weight, while also reducing circulating testosterone levels. Based on these results and reports in the literature, we hypothesize that PC-SPES has potent antiandrogenic effects that are exerted at several potential sites (e.g., CNS, testis, and prostate), and through several potential mechanisms (e.g., androgen synthesis, receptor activation, or metabolism). In this way, the individual herbal components of PC-SPES may act synergistically to exert anti-tumor actions that may be more effective than those produced by any single treatment modality or site of action. Thus, it is our intention to study the mechanism of action of PC-SPES in all of its complexity rather than examine the biological actions of its individual components. Our work will identify the sites and potential antiandrogenic actions of PC-SPES, which are undoubtedly causal factors in its apparent anti-tumor effects. To test our hypothesis, we will employ biochemical and histological techniques together with an HPLC-analyzed preparation of PC-SPES to systematically address the following specific aims:
Specific Aim 1 : To evaluate the time- and dose-dependent effects of orally administered PC-SPES on prostate weight and histology and on sex steroid and gonadotropin levels, in an effort to elucidate the potential mechanism(s) of action of PC-SPES on prostate growth and pathology.
Specific Aim 2 : To correlate the effects of PC-SPES on prostate growth with 5a-reductase, aromatase, and androgen receptor concentrations, in order to determine the level(s) at which PC-SPES interacts with the androgen-signaling pathway.
Specific Aim 3 : To evaluate the effect of PCSPES on Cytochrome P450-mediated metabolism of androgenic and antiandrogenic drugs by the liver, in order to identify possible interactions of PC-SPES with other hormone therapies.
| Wadsworth, Teri L; Carroll, Julie M; Mallinson, Rebecca A et al. (2004) Saw palmetto extract suppresses insulin-like growth factor-I signaling and induces stress-activated protein kinase/c-Jun N-terminal kinase phosphorylation in human prostate epithelial cells. Endocrinology 145:3205-14 |
| Wadsworth, Teri; Poonyagariyagorn, Hataya; Sullivan, Elinore et al. (2003) In vivo effect of PC-SPES on prostate growth and hepatic CYP3A expression in rats. J Pharmacol Exp Ther 306:187-94 |
