https://scholars.lib.ntu.edu.tw/handle/123456789/541993
標題: | Desipramine-induced apoptosis in human PC3 prostate cancer cells: Activation of JNK kinase and caspase-3 pathways and a protective role of [Ca2+]i elevation | 作者: | HONG-CHIANG CHANG Huang C.-C. Huang C.-J. Cheng J.-S. Liu S.-I. Tsai J.-Y. Chang H.-T. Huang J.-K. Chou C.-T. Jan C.-R. |
關鍵字: | Apoptosis; Caspase-3; Desipramine; MAPKs; PC3 cells; Prostate | 公開日期: | 2008 | 卷: | 250 | 期: | 1 | 起(迄)頁: | 9��14�� | 來源出版物: | Toxicology | 摘要: | The antidepressant desipramine has been shown to induce a rise in cytosolic Ca2+ levels ([Ca2+]i) and cytotoxicity in human PC3 prostate cancer cells, but the mechanisms underlying its cytotoxic effect is unclear. Cell viability was examined by WST-1 assays. Apoptosis was assessed by propidium iodide staining and an increase in caspase-3 activation. Phosphorylation of protein kinases was analyzed by immunoblotting. Desipramine caused cell death via apoptosis in a concentration-dependent manner. Immunoblotting data revealed that desipramine activated the phosphorylation of c-Jun NH2-terminal kinase (JNK), but not extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK). SP600125 (a selective JNK inhibitor) partially prevented cells from apoptosis. Pretreatment with BAPTA/AM, a Ca2+ chelator, to prevent desipramine-induced [Ca2+]i rises worsened desipramine-induced cytotoxicity. Immunoblotting data suggest that BAPTA/AM pretreatment enhanced desipramine-evoked JNK phosphorylation and caspase-3 cleavage. The results suggest that in PC3 cells, desipramine caused apoptosis via inducing JNK-associated caspase-3 activation, and [Ca2+]i rises may slow down or alleviate desipramine-induced cytotoxicity. ? 2008 Elsevier Ireland Ltd. All rights reserved. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-47849107996&doi=10.1016%2fj.tox.2008.05.010&partnerID=40&md5=fafb035b41bd9ef9dee27c68c5e93a4d https://scholars.lib.ntu.edu.tw/handle/123456789/541993 |
ISSN: | 0300-483X | DOI: | 10.1016/j.tox.2008.05.010 | SDG/關鍵字: | anthra[1,9 cd]pyrazol 6(2h) one; calcium; caspase 3; desipramine; mitogen activated protein kinase p38; stress activated protein kinase; apoptosis; article; cancer cell; cell viability; controlled study; drug activity; human; human cell; immunoblotting; priority journal; prostate cancer; protein phosphorylation; Antidepressive Agents, Tricyclic; Apoptosis; Calcium; Caspase 3; Cell Line, Tumor; Cell Survival; Cytosol; Desipramine; Dose-Response Relationship, Drug; Humans; Immunoblotting; JNK Mitogen-Activated Protein Kinases; Male; Phosphorylation; Prostatic Neoplasms |
顯示於: | 醫學系 |
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