Previous animal studies examining dietary selenium effects on prostatic carcinogenesis did

Previous animal studies examining dietary selenium effects on prostatic carcinogenesis did not show preventive benefit including one study in a rat model involving testosterone (T) and estradiol (E2)-induced prostatic oxidative stress. prostatic sites of T+E2-induced preneoplasia (p<0.05) but selenomethionine did not attenuate 8-OHdG staining and dysplasia in the lateral prostate. Glutathione-peroxidase activity and mRNA expression were induced by T+E2 (p<0.05-p<0.0001) but not changed by selenomethionine. Selenomethionine did not cause significant responses in expression and activity of glutathione-peroxidase and MnSOD except for a reduction of MnSOD protein expression in the lateral prostate (p<0.01). The absence of reduction of oxidative stress and dysplasia and the minimal effects on antioxidant enzymes caused by selenomethionine are consistent with the null effects observed in selenium supplementation animal studies and clinical trials. Significant (p<0.01) opposite apoptosis/cell proliferation balance responses to selenomethionine and to T+E2 occurred in the lateral and dorsal prostate explaining why T+E2 induces lesions selectively in the lateral lobe of NBL rats. INTRODUCTION Prostate cancer is the most common noncutaneous malignancy and one of the major causes of cancer-related death in men in the western world [1]. No risk factors offer opportunities for primary prevention of this malignancy [2]. Chemoprevention i.e. the inhibition or reversal of the development or progression of cancer by chemicals bioactive plant compounds or dietary components is a mechanism-based attractive and potentially powerful approach to prostate cancer prevention [2]. Inflammatory processes known to involve oxidative damage are suspected to be associated with human prostate cancer [3 4 and the presence of the oxidized DNA base 8-hydroxy-2′-deoxyguanosine (8-OHdG) has been observed in human prostate tissue [5]. The use of selenium compounds has long been considered a promising approach to chemoprevention [6]. Although the mechanisms of chemoprevention by selenium are not precisely understood several theories have emerged. Among these selenium metabolites have been postulated to selectively promote apoptosis and inhibit proliferation of cancer cells. It has also been proposed that selenium supplementation of individuals with low selenium status may increase the expression of antioxidant selenoproteins and thereby prevents DNA damage that could lead to mutations and Delphinidin chloride subsequent carcinogenesis [6-8]. Epidemiological studies of Delphinidin chloride serum/plasma or toenail selenium levels have supported a protective role of selenium against prostate cancer (9) but studies examining selenium intake or use of selenium supplements in clinical trials or cohort or case-control studies did not [9-12]. Analysis of data from the Nutritional Prevention of Cancer clinical trial with selenized yeast in men at increased risk for skin cancer [13] Esr1 yielded evidence to suggest that supplementation with this type of selenium in men with low selenium status at baseline may be protective against prostate cancer as a secondary endpoint [14]. However three subsequent large randomized clinical trials of selenium supplementation with prostate cancer as Delphinidin chloride the primary endpoint did not find preventive efficacy of selenium. Selenized yeast did not prevent prostate cancer in a phase III trial with men with elevated prostate-specific antigen levels or suspect rectal exam but negative prostate biopsies [15]. Selenomethionine (200 μg as selenium) was not protective in two large randomized clinical trials the SELECT study in average risk men (alone or with α-tocopherol at 400 IU/day) [16] and the SWOG S9917 trial with high-risk men diagnosed with high grade prostatic intraepithelial neoplasia (PIN) [17]. Of note none of these studies included an analysis stratifying participants by baseline selenium status as was previously carried out on the results of the Nutritional Prevention of Cancer clinical trial [14]. Previous studies with selenomethionine or selenized yeast in animal models of prostate carcinogenesis have been negative including experiments with tumor induction models [18 19 Selenomethionine and most other selenium compounds also do not affect Delphinidin chloride the.