#A180 Selenium Specifically Inhibits Protein Kinase C in Prostate Epithelial Cells Promoted by Lipid Hydroperoxides – Mechanism for Selective Cytotoxicity to Precancer Cells. Rayudu Gopalakrishna, Usha Gundimeda, USC School of Medicine, Los Angeles, CA. Besides scavenging free radicals, antioxidants such as selenium inhibit cell signaling and inhibit tumor promotion. However, it is not clear how selenium interferes with cell signaling selectively in precancer cells without causing toxicity to host. Methylselenol was previously postulated as the active metabolite that mediates cancer-preventive actions of selenium. Nevertheless, it is a volatile compound and its mechanism of action, especially that occurring at the tissue available low concentrations, is not known. We have previously shown that redox-active selenocompounds directly inactivate protein kinase C (PKC) by inducing sulfhydryl oxidation. Since selenium is required at low concentrations to inhibit tumor promotion, it is possible that the oxidants present in the promoting cells may enhance cellular retention and the preventive actions of volatile methylselenol by oxidizing it to methylseleninic acid. Benzeneselenol and methylselenol at catalytically low concentrations induced an inactivation of PKC only in the presence of peroxides such as arachidonic acid hydroperoxide. By reducing peroxides, selenol is oxidized to seleninic acid, which in turn oxidized protein sulfhydryls and thus reduced back to selenol. Although this peroxidatic redox-cycling process nonspecifically oxidizes many thiols including glutathione, the lipophilic selenols by reacting with lipid peroxides present within the membrane can specifically oxidize sulfhydryls of key membrane-bound enzymes such as PKC. Immortalized human prostate epithelial (RWPE-1) cells pretreated with N-methyl-N-nitrosourea were promoted by lipid hydroperoxides as evidenced by a growth in soft agar. Selenometabolites at low (200 nM) concentration inhibited peroxide-induced tumor promotion in this model. Only in the presence of lipid peroxides, selenium induced inactivation of PKC alpha and apoptosis in the precancer prostate cells. Therefore, selenium per se at low concentration may not induce cell death rather it blocks the escape of precancer cells from peroxide-induced cell death and thus restores cell death. Conceivably, reaction of selenols with tumor-promoting peroxides provides one of the specific mechanisms by which cancer-preventive selenocompounds interfere with signaling selectively in the promoting cells but not in the normal cells. Frontiers in Cancer Prevention Research, 2003 AACR Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. Support our work with any size DONATION - see left side of any page - for how to donate. You can help raise awareness of CAM.