Title |
Up-regulation of 5-lipoxygenase by inhibition of cathepsin G enhances TRAIL-induced apoptosis through down-regulation of survivin
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Published in |
Oncotarget, November 2017
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DOI | 10.18632/oncotarget.22508 |
Pubmed ID | |
Authors |
Seon Min Woo, Kyoung-Jin Min, Seung Un Seo, Shin Kim, Jong-Wook Park, Dae Kyu Song, Hyun-Shik Lee, Sang Hyun Kim, Taeg Kyu Kwon |
Abstract |
Cathepsin G is a serine protease secreted from activated neutrophils, it has important roles in inflammation and immune response. Moreover, cathepsin G promotes tumor cell-cell adhesion and migration in cancer cells. In this study, we investigated whether inhibition of cathepsin G could sensitize TRAIL-mediated apoptosis in cancer cells. An inhibitor of cathepsin G [Cathepsin G inhibitor I (Cat GI); CAS 429676-93-7] markedly induced TRAIL-mediated apoptosis in human renal carcinoma (Caki, ACHN, and A498), lung cancer (A549) and cervical cancer (Hela) cells. In contrast, combined treatment with Cat GI and TRAIL had no effect on apoptosis in normal cells [mesangial cell (MC) and human skin fibroblast (HSF)]. Cat GI induced down-regulation of survivin expression at the post-translational level, and overexpression of survivin markedly blocked apoptosis induced by combined treatment with Cat GI plus TRAIL. Interestingly, Cat GI induced down-regulation of survivin via 5-lipoxygenase (5-LOX)-mediated reactive oxygen species (ROS) production. Inhibition of 5-LOX by gene silencing (siRNA) or a pharmacological inhibitor of 5-LOX (zileuton) markedly attenuated combined treatment-induced apoptosis. Taken together, our results indicate that inhibition of cathepsin G sensitizes TRAIL-induced apoptosis through 5-LOX-mediated down-regulation of survivin expression. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 19 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Master | 3 | 16% |
Researcher | 3 | 16% |
Student > Bachelor | 2 | 11% |
Student > Ph. D. Student | 2 | 11% |
Other | 1 | 5% |
Other | 2 | 11% |
Unknown | 6 | 32% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 4 | 21% |
Agricultural and Biological Sciences | 4 | 21% |
Medicine and Dentistry | 2 | 11% |
Pharmacology, Toxicology and Pharmaceutical Science | 1 | 5% |
Veterinary Science and Veterinary Medicine | 1 | 5% |
Other | 2 | 11% |
Unknown | 5 | 26% |