Endoplasmic Reticulum Stress Signaling Pathways Is Involved in Trichosanthin-Induced Apoptosis in Human Cervical Cancer Cell Line Hela

Abstract

Endoplasmic reticulum stress(ERS)is a kind of sub-cellular pathological process which result from calcium disorderliness and protein improper folding. And endoplasmic reticulum stress induced apoptosis is a novel pathway which different from the mitochondria-initiated intrinsic pathway and the death receptor-triggered extrinsic pathway. Trichosanthin (TCS), a type I ribosome-inactivating protein, induces cell death in various cell types including several tumor cell lines. However, the mechanism remains largely uncharacterized. The aim of present study is to explore possible mechanism underlying its cytotoxicity by using human cervical cancer Hela cell line as a model. We found that TCS induced apoptosis in Hela cells in a time- and dose- dependent manner. cDNA microarray analysis demonstrated that there were 62 pieces of gene up-regulated and 16 pieces of gene down-regulated after treated with TCS, subsequent analysis by RT-PCR and western blot confirmed that GRP78 and calpain could be significantly induced by TCS , which strongly supported the involvement of endoplasmic reticulum stress pathway in TCS-induced apoptosis. This study reveals a new pathway of endoplamic reticulum stress in TCS induces apoptosis in hela cells, Further research with more cell lines and calpain inhibitor needs to be performed to determine if calpian activation is a common feature in TCS-induced apoptosis.