Arsenic suppresses necrosis induced by selenite in human leukemia HL-60 cells

Selenium, an essential trace element for humans, has been shown to have anticancer effects. Arsenic, a possibly essential ultratrace element for humans, has been used in the treatment of leukemia. Anticancer effects of selenium and arsenic have been related to their ability to induce apoptosis. Because humans are exposed to diverse trace elements simultaneously, it is important to learn their interrelationship. In this study, we demonstrate that sodium selenite (Na2SeO3) causes apoptosis at 3 muM and necrosis at high concentrations (> 3 muM) in HL-60 cells. Similarly, both sodium arsenite (NaAsO2) at 50 muM and sodium arsenate (Na2HAsO4) induce apoptosis at 500 muM and necrosis at higher concentrations (> 50 muM and > 500 muM, respectively) in HL-60 cells. Arsenite/arsenate, but not selenite, enhances AP-1 DNA-binding activity. This finding indicates different mechanisms through which apoptosis is induced by these two elements. Interestingly, we observed that HL-60 cell necrosis induced by a high concentration (> 3 muM) of selenite was essentially inhibited by arsenic (50,um of NaAsO2 or 500 muM of Na2HAsO4), which resulted in a net effect of apoptosis. Because AP-1 DNA-binding activity was not induced in the presence of a combination of necrotic amount of selenite and apoptotic amount of arsenite/arsenate, the observed apoptosis apparently was through the mechanism used by selenite. Our results suggest, for the first time, that the toxic necrotic effect of selenite can be neutralized by arsenite/arsenate at the cellular level.