In vivo effect of PC-SPES on prostate growth and hepatic CYP3A expression in rats.
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.
Wadsworth
Teri
T
Department of Physiology and Pharmacology L334, Oregon Health and Science University, 3181 SW Sam Jackson Park Rd., Portland, OR 97239-3098, USA.
Poonyagariyagorn
Hataya
H
Sullivan
Elinore
E
Koop
Dennis
D
Roselli
Charles E
CE
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004365:Drugs, Chinese Herbal; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D006062:Gonadotropins / Q000378:metabolism; D006801:Humans; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D011467:Prostate / Q000187:drug effects* / Q000502:physiology; D011471:Prostatic Neoplasms / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013256:Steroids / Q000378:metabolism; D014599:Uterus / Q000187:drug effects / Q000502:physiology
D000972:Antineoplastic Agents, Phytogenic; D004365:Drugs, Chinese Herbal; D006062:Gonadotropins; D010936:Plant Extracts; D012333:RNA, Messenger; D013256:Steroids; C114209:herbal preparation PC-SPES; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; D051544:Cytochrome P-450 CYP3A; D010089:Oxidoreductases, N-Demethylating