Sodium Arsenite Down Regulates XIAP Expression Through Post-transcriptional Level And Induces Cell Death In HCC

The X-chromosome linked inhibitor of apoptosis (XIAP) has been reported to be elevated in many types of cancers and meanwhile associated with the malignancy of cancer. In this study, we have investigated whether XIAP, the most studied member of IAP family, is a target for sodium arsenite (NaAsO2)-induced cytotoxicity and cell death. Exposure of three human hepatocellular carcinoma (HCC) cell lines-Huh7,7402, SK-HEP1to NaAsO2resulted in a time dependent decrease of XIAP expression. Additional studies conducted to understand the potential mechanisms responsible for NaAsO2-induced inhibition of XIAP expression demonstrated that exposure to sodium arsenite resulted in translational down regulation of XIAP expression, probably through phosphorylation of eIF2a. Conversely, overexpression of XIAP can partially reverse the cytotoxicity induced by arsenite. Analysis of HCC tissue also confirmed that the up-regulation of XIAP was through post-transcriptional level. Collectively, our data demonstrate that sodium arsenite reduces the XIAP expression through translational regulation, especially by phosphorylation of eIF2a. Therefore, it has the potential to be effective in HCC therapy.