Resveratrol suppresses prostate cancer progression in transgenic mice.
Resveratrol, a natural polyphenolic phytochemical, has been reported to act as an antioxidant and provide anticancer activities. We hypothesized that resveratrol would exert a chemopreventive effect against prostate cancer via regulation of sex steroid receptor and growth factor signaling pathways. In the current study, Transgenic Adenocarcinoma Mouse Prostate males were fed resveratrol (625 mg resveratrol per kg AIN-76A diet) or phytoestrogen-free, control diet (AIN-76A) starting at 5 weeks of age. Mechanisms of action and histopathology studies were conducted at 12 and 28 weeks of age, respectively. Resveratrol in the diet significantly reduced the incidence of poorly differentiated prostatic adenocarcinoma by 7.7-fold. In the dorsolateral prostate, resveratrol significantly inhibited cell proliferation, increased androgen receptor, estrogen receptor-beta, and insulin-like growth factor-1 receptor, and significantly decreased insulin-like growth factor (IGF)-1 and phospho-extracellular regulating kinase 1 (phospho-ERK 1). In the ventral prostate, resveratrol significantly reduced cell proliferation and phospho-ERKs 1 and 2, but did not significantly alter insulin-like growth factor-1 receptor and IGF-1. Serum total testosterone, free testosterone, estradiol, dihydrotestosterone and sex hormone-binding globulin (SHBG) concentrations and Simian Virus-40 large T antigen expression in the prostate were not altered in resveratrol-treated mice. Total resveratrol concentration in the blood serum of 12-week-old mice treated for 3 weeks with 625 mg resveratrol per kg diet was 52 +/- 18 nM. The decrease in cell proliferation and the potent growth factor, IGF-1, the down-regulation of downstream effectors, phospho-ERKs 1 and 2 and the increase in the putative tumor suppressor, estrogen receptor-beta, provide a biochemical basis for resveratrol suppressing prostate cancer development.
Department of Pharmacology and Toxicology, University of Alabama at Birmingham, 1670 University Boulevard, Birmingham, AL 35294-0019, USA.
Curt E
CE
Harper
Brijesh B
BB
Patel
Jun
J
Wang
Alireza
A
Arabshahi
Isam A
IA
Eltoum
Coral A
CA
Lamartiniere
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000097:blood / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects; D003433:Crosses, Genetic; D018450:Disease Progression; D005260:Female; D006579:Heterozygote; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000077185:Resveratrol; D013267:Stilbenes / Q000097:blood / Q000627:therapeutic use*
D000972:Antineoplastic Agents, Phytogenic; D013267:Stilbenes; D000077185:Resveratrol