Z-FL-COCHO, a cathepsin S inhibitor, enhances oxaliplatin-induced apoptosis through upregulation of Bim expression.

Biochem Biophys Res Commun 2018 04 13;498(4):849-854. Epub 2018 Mar 13.

Department of Immunology, School of Medicine, Keimyung University, Dalseo-Gu, Daegu, South Korea. Electronic address:

Inhibition of cathespsin S not only inhibits invasion and angiogenesis, but also induces apoptosis and autophagy in cancer cells. In present study, we revealed that pharmacological inhibitor [Z-FL-COCHO (ZFL)] of cathepsin S up-regulates pro-apoptotic protein Bim expression at the posttranslational levels. These effects were not associated with MAPKs and AMPK signal pathways. Interestingly, pretreatment with the chemical chaperones (TUDCA and PBA) and knockdown of protein phosphatase 2A (PP2A) markedly inhibited ZFL-induced Bim upregulation. ZFL enhances oxaliplatin-mediated apoptosis through ER stress-induced Bim upregulation in cancer cells. Collectively, our results suggest that inhibition of cathepsin S-induced Bim upregulation contribute to anti-cancer drug-induced apoptotic cell death in renal carcinoma Caki cells.

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http://dx.doi.org/10.1016/j.bbrc.2018.03.068DOI Listing
April 2018

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