Cathepsin L mediates resveratrol-induced autophagy and apoptotic cell death in cervical cancer cells

• DOI: 10.4161/auto.5.4.7666
• Publication Date: 2009-12-15T16:31:08Z
• Authors: Keng-Fu Hsu; Chao-Liang Wu; Soon-Cen Huang; Ching-Ming Wu; Jenn-Ren Hsiao; Yi-Te Yo; Yu-Hung Chen; Ai-Li Shiau; Cheng-Yang Chou
• Keywords: Pepstatin; Cathepsin L; Antipain

Cathepsins have long been considered as housekeeping molecules. However, specific functions also attributed to each of these lysosomal proteases. Squamous cell carcinoma antigen (SCCA) 1, widely expressed in various uterine cervical cells, is an endogenous cathepsin (cat) L inhibitor. In this study, we investigated whether the cat L-SCCA 1 pathway and autophagy were involved resveratrol (RSV)-induced cytotoxicity cancer cells. RSV induced GFP-LC3 aggregation well increased presence LC3-II autophagosomes was revealed by electron microscopy Prolonged treatment cytosolic translocation cytochrome c, caspase 3 activation apoptotic death. This effect abrogated trans-epoxysuccinyl-L-leucylamido-(4-guanidino)butane, inhibitor B L, but not pepstatin A, D. As cells express little B, further studied role L. dissipation membrane permeability (LMP), leakage expression activity Inhibition small interference RNA (siRNA) protected from RSV-induced cytotoxicity. contrast, inhibition SCCA siRNA promoted autophagic response wortmannin (WT) or asparagine (ASP) resulted decreased early formation, reduced LMP, abolishment increase conclusion, identified a new cytotoxic mechanism which enzyme acts death signal integrator Furthermore, may play antiapoptotic through anti-cat activity.