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

Authors
Seung Un SeoSeon Min WooKyoung-jin MinTaeg Kyu Kwon
Department
Dept. of Immunology (면역학)
Issue Date
2018
Citation
Biochemical and Biophysical Research Communications, Vol.498(4) : 849-854, 2018
ISSN
0006-291X
Abstract
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.
Keywords
ApoptosisBimCathepsin SER stressOxaliplatinPP2A
URI
http://kumel.medlib.dsmc.or.kr/handle/2015.oak/41583
Appears in Collections:
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
Keimyung Author(s)
권택규
Full Text
https://linkinghub.elsevier.com/retrieve/pii/S0006-291X(18)30546-1
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