Page 14 - F. Cell biology

[F. Cell biology-7]

RIP1 silencing sensitizes arsenite-induced necroptotic cell

death in L929 cells

Su Bin Sin¹, Young Sik Cho¹˙*

¹College of Pharmacy, Keimyung University, Daegu 42601, Republic of Korea

Arsenic compounds such as sodium arsenite (SA) and arsenic trioxide (ATO) have been known to be cytotoxic.
Primarily, in this study, we aimed to outline the cell death modes caused by arsenic compounds and to address
what proteins would be responsible for arsenite-induced cytotoxicity. Both SA and ATO substantially exhibited

cytotoxic activity in L929 cells. However, necrostatin-1 (Nec-1) treatment significantly reversed cell death mediated

by arsenic compounds, suggesting that cells are committed to die in a programmed necrotic way. Using interfering
RNAs, furthermore, we found that RIP1 knockdown rendered more sensitive to SA than mock group, and that RIP3
knockdown had an antagonizing effect on SA cytotoxicity. SA cytotoxicity was closely correlated with intracellular

ROS production. Therefore, it is proposed that RIP1 downregulation promotes necroptotic cell death of arsenic
compounds in L929.