کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2113907 1084506 2010 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Up-regulation of death receptor 4 and 5 by celastrol enhances the anti-cancer activity of TRAIL/Apo-2L
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
Up-regulation of death receptor 4 and 5 by celastrol enhances the anti-cancer activity of TRAIL/Apo-2L
چکیده انگلیسی

Our previous study demonstrated that celastrol combined with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/Apo-2L) exhibited significant synergistic anti-cancer activities, thus we were promoted to investigate the molecular mechanism of this synergy. Here in this study, we show that celastrol up-regulates death receptor 4 (DR4) and 5 (DR5) expression at mRNA, total protein and cell surface levels, and the specific knockdown using DR4- or DR5-targeting siRNA transfection attenuates the PARP cleavage caused by the combination of celastrol and TRAIL/Apo-2L, denoting the critical roles of DR induction in this sensitization. Of note is that although celastrol activates p38 mitogen activated protein kinases (p38 MAPK), SB203580, one specific inhibitor of p38, fails to interrupt celastrol-induced DR4 expression and the enhanced apoptosis caused by celastrol plus TRAIL/Apo-2L. In addition, the protein expression of Mcl-1 and FLIP, two critical antiapoptotic factors, is not decreased upon celastrol treatment under our experimental conditions. Taken together, the present study demonstrates that the enhanced mRNA and protein expression of DR4 and DR5 play prominent roles in the sensitization of celastrol to TRAIL/Apo-2L-induced apoptosis, in a p38 MAPK-independent manner.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cancer Letters - Volume 297, Issue 2, 28 November 2010, Pages 155–164
نویسندگان
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