Emily C Chiang, David G Bostwick, David J Waters
Selenium has received considerable attention as a cancer preventive agent. But the puzzling, disquieting results of the Selenium and Vitamin E Cancer Prevention Trial (SELECT) have called into question how much is really understood about the biology behind selenium and cancer risk. This predicament should provide researchers with a renewed stimulus for exploring mechanisms of selenium anti-carcinogenesis. One such line of inquiry is homeostatic housecleaning — that selenium can preferentially eliminate DNA-damaged cell populations through apoptosis, consistent with the decreased DNA damage and increased apoptosis observed in the prostate of selenium-replete dogs after receiving additional dietary selenium supplementation. Because growing experimental evidence suggests the anti-carcinogenic effects of selenium on prostatic cells are form-dependent and apoptosis is a DNA damage response, the aim of this research was to determine whether selenite, a form of selenium that induces DNA damage, possesses potent homeostatic housecleaning activity. To test this hypothesis, we exposed human and canine prostate cancer cells to non-cytotoxic concentrations of hydrogen peroxide (H2O2) to create cell populations with higher levels of oxidant-induced DNA damage, and then evaluated the extent to which oxidant damage sensitizes prostate cancer cell populations to selenite-triggered apoptosis compared to apoptosis triggered by methylseleninic acid (MSA), a non-DNA damaging methylselenol precursor we previously showed to have strong homeostatic housecleaning activity. In this brief communication, we report that non-cytotoxic oxidant-induced damage does not sensitize prostate cancer cell populations to selenite-triggered apoptosis. Intensity of apoptosis triggered by MSA in H2O2-damaged prostate cancer cells was 3 times higher than undamaged cell populations not exposed to H2O2 (P ≤ 0.01). In contrast, neither human nor canine prostate cancer cells with oxidant-induced damage had a significant increase in intensity of selenite-triggered apoptosis compared to undamaged cells. The divergent results between MSA and selenite in our experiments contribute to a growing catalogue of observations that suggest there are important form-dependent differences in the extent to which selenium can impact the emergence of prostate cancer. By carefully documenting the form-dependent biological effects of selenium and other nutrients, we commit ourselves to more precisely qualifying the implications of laboratory results and to more carefully designing and interpreting the results of large-scale human trials.
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