QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.102.048645v1 306/1/187    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Wadsworth, T. Articles by Roselli, C. E. Search for Related Content PubMed PubMed Citation Articles by Wadsworth, T. Articles by Roselli, C. E. Pubmed/NCBI databases Substance via MeSH

TOXICOLOGY

In Vivo Effect of PC-SPES on Prostate Growth and Hepatic CYP3A Expression in Rats

Department of Physiology and Pharmacology, Oregon Health and Science University, Portland, Oregon

PC-SPES, a proprietary mixture composed of eight different herbs, is used worldwide as an alternative treatment by prostate cancer patients. It has been suggested that the clinical and in vitro antitumor activity exhibited by PC-SPES may be due to estrogenic activity, which in turn may be mediated by the presence of undeclared prescription drug contaminants. Here, we evaluated the in vivo effects of two different commercial lots of PC-SPES in male and female rats. Our high-pressure liquid chromatography analysis coupled with gas chromatography/mass spectrometry analysis by an independent laboratory suggested that PC-SPES lot 5430125 was contaminated with diethylstilbestrol (DES), whereas lot 5431249 was not. Treatment of male rats with PC-SPES lot 5430125 or DES alone reduced the weight of androgen target organs and decreased circulating levels of sex steroids and luteinizing hormone, whereas lot 5431249 was without effect. In addition, lot 5430125 and DES, but not lot 5431249 increased uterine weight in female rats. These results suggest that the inhibitory effects on androgen targets are mediated through suppression of the hypothalamic-pituitary axis and this suppression is probably due to DES contamination. We assessed the effects of both lots of PC-SPES and DES on hepatic cytochrome P450 expression and activity. Both lots of PC-SPES and DES reduced CYP3A activity and protein levels. Because the response of CYP3A to PC-SPES was not dependent on whether it contained DES, a phytochemical component of PC-SPES is most likely responsible for this effect. Inhibition of CYP3A has important implications for potential herbal-drug interactions.

Address correspondence to: Dr. Charles E. Roselli, Department of Physiology and Pharmacology L334, Oregon Health and Science University, 3181 SW Sam Jackson Park Rd., Portland, OR 97239-3098. E-mail: rosellic{at}ohsu.edu