期刊
JOURNAL OF CELLULAR BIOCHEMISTRY
卷 112, 期 1, 页码 118-127出版社
WILEY
DOI: 10.1002/jcb.22896
关键词
DIALLYL TRISULFIDE; REACTIVE OXYGEN SPECIES; ASK1; JNK; BIM
资金
- NCI [CA121395, CA140554]
- Susan G. Komen Breast Cancer Foundation [BCTR60306]
- NATIONAL CANCER INSTITUTE [R01CA140554, R03CA121395] Funding Source: NIH RePORTER
The aim of this study was to investigate the effect of garlic constituent diallyl trisulfide (DATS) on the cell-death signaling pathway in a human breast cell line (MDA-MB-231). We observed that DATS (10-100 mu M) treatment resulted in dose-and time-dependent cytotoxicity. Treatment of MDA-MB-231 cells with a cytotoxicity inducing concentration of DATS (50-80 mu M) resulted in an increase in the intracellular level of reactive oxygen species (ROS). Data from assay with MitoSOX (TM) Red reagent suggest that mitochondria are the main source of ROS generation during DATS treatment. DATS-induced oxidative stress was detected through glutaredoxin (GRX), a redox-sensing molecule, and subsequently GRX was dissociated from apoptosis signal-regulating kinase 1 (ASK1). Dissociation of GRX from ASK1 resulted in the activation of ASK1. ASK1 activated a downstream signal transduction JNK (c-Jun N-terminal kinase)-Bim pathway. SP600125, a JNK inhibitor, inhibited DATS-induced Bim phosphorylation and protected cells from DATS-induced cytotoxicity. Our results indicate that the cytotoxicity caused by DATS is mediated by the generation of ROS and subsequent activation of the ASK1-JNK-Bim signal transduction pathway in human breast carcinoma MDA-MB-231 cells. J. Cell. Biochem. 112: 118-127, 2011. (C) 2010 Wiley-Liss, Inc.
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