Null Activity of Selenium and Vitamin E as Cancer Chemopreventive Agents in the Rat Prostate

Abstract

To evaluate the potential efficacy of selenium and vitamin E as inhibitors of prostate carcinogenesis, four chemoprevention studies using a common protocol were done in a rat model of androgen-dependent prostate cancer. After stimulation of prostate epithelial cell proliferation by a sequential regimen of cyproterone acetate followed by testosterone propionate, male Wistar-Unilever rats received a single i.v. injection of N-methyl-N-nitrosourea (MNU) followed by chronic androgen stimulation via subcutaneous implantation of testosterone pellets. At 1 week post-MNU, groups of carcinogen-treated rats (39-44/group) were fed either a basal diet or a basal diet supplemented with L-selenomethionine (3 or 1.5 mg/kg diet; study 1), DL-α-tocopherol (vitamin E, 4,000 or 2,000 mg/kg diet; study 2), L-selenomethionine + vitamin E (3 + 2,000 mg/kg diet or 3 + 500 mg/kg diet; study 3), or selenized yeast (target selenium levels of 9 or 3 mg/kg diet; study 4). Each chemoprevention study was terminated at 13 months post-MNU, and prostate cancer incidence was determined by histopathologic evaluation. No statistically significant reductions in prostate cancer incidence were identified in any group receiving dietary supplementation with selenium and/or vitamin E. These data do not support the hypotheses that selenium and vitamin E are potent cancer chemopreventive agents in the prostate, and when considered with the recent clinical data reported in the Selenium and Vitamin E Cancer Prevention Trial (SELECT), show the predictive nature of this animal model for human prostate cancer chemoprevention. Cancer Prev Res; 3(3);

Effect of Selenium on Carbimazole-Induced Histopathological and Histochemical Alterations in Prostate of Albino Rats

“…Recent studies have noted an inverse relationship between selenium status and cancer risk in several tissues, including the esophagus, stomach, lung, and prostate [11]. McCormick et al [12] did not support the hypotheses that selenium is potent cancer chemopreventive agent in the prostate of rat. Liao et al [13] reported that selenium played a beneficial role for prevention of cisplatin hepatotoxicity in mice.…”

A Perspective on Prostate Carcinogenesis and Chemoprevention

“…Selenomethionine and selenized yeast were also negative in studies with rat models of prostate cancer [60, 61]. In one of these studies, α-tocopherol increased the incidence of prostate cancer, similar to the results of SELECT [60]. We found that selenium at physiological concentrations increased cell proliferation in LNCaP prostate cancer cells in vitro, but inhibited proliferation at higher doses [62].…”

“…Selenomethionine did not affect risk of progression to prostate cancer in men with high grade prostatic intraepithelial neoplasia (PIN) [58] and selenized yeast did not affect risk in men with elevated PSA or other high risk indicators who were negative on biopsy [59]. Selenomethionine and selenized yeast were also negative in studies with rat models of prostate cancer [60, 61]. In one of these studies, α-tocopherol increased the incidence of prostate cancer, similar to the results of SELECT [60].…”

Cancer chemoprevention research with selenium in the post-SELECT era: Promises and challenges

“…For the former category, a couple of studies conducted in the late 1990’s before SELECT did not find any efficacy of SeMet and α-tocopheryl acetate alone or in combination or of Se-yeast on a prostate carcinogenesis model in rats. These negative results were initially communicated in meeting proceedings and the full results were only published after SELECT results had been published (38) (39). In one study, the potential of SeMet and α-tocopheryl acetate was examined to modulate PCa development in testosterone plus estradiol-treated Noble (NBL/Crl) rats, a model that involves sex hormone-induced oxidative stress and prostatic inflammation (39).…”