Modulation of the Arsenic Effects on Cytotoxicity, Viability, and Cell Cycle in Porcine Endothelial Cells by Selenium

Abstract

The differential effects of arsenic compounds and the effect of selenium on arsenic-induced changes in cytotoxicity, viability, and cell cycle of porcine aorta endothelial cells (PAECs) were investigated. MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) assay indicated that arsenic trioxide (As(2)O(3)) and sodium arsenite (NaAsO(2)) showed similar cytotoxicity, whereas sodium arsenate (Na(2)HAsO(4)) did not show cytotoxicity in PAECs. As(2)O(3) and NaAsO(2) at 20 microM decreased PAEC viability, decreased G0/G1 phase, and increased apoptosis. An increased G2/M phase was observed in NaAsO(2)-treated PAECs, whereas an increase in secondary necrosis (late apoptosis) was observed in As(2)O(3)-treated PAECs. As(2)O(3)-induced apoptosis was associated with upregulation of p53 and caspase 3, whereas NaAsO(2)-induced apoptosis was associated with p53 upregulation. Sodium selenite (Na(2)SeO(3)) at 1 nM reduced 20 microM As(2)O(3)-induced cytotoxicity, but not apoptosis, at 24 h. Increased glutathione peroxidase (GPX) activity by Na(2)SeO(3) pretreatment in 20 microM As(2)O(3)-treated PAECs suggests that Na(2)SeO(3) modulates As(2)O(3)-induced cytoxicity by GPX modulation.