کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5824163 | 1118435 | 2011 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Mcl-1 downregulation by YM155 contributes to its synergistic anti-tumor activities with ABT-263
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کلمات کلیدی
PARPABT-263XIAPYM155SurvivinSTAT3IAPMcl-1DMSO - DMSODimethyl sulfoxide - دیمتیل سولفواکسیدNSCLC - سرطان ریوی غیر سلول کوچکNon-small cell lung cancer - سرطان غیر سلول کوچک ریهsignal transducer and activator of transcription 3 - مبدل سیگنال و فعال کننده رونویسی 3Cell death - مرگ سلولی inhibitors of apoptosis - مهارکننده های آپوپتوزX-linked Inhibitor of Apoptosis Protein - پروتئین آپوپتوز وابسته به X-linkedpoly (ADP-ribose) polymerase - پلی (ADP-ribose) پلیمراز
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
داروشناسی
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چکیده انگلیسی
YM155, a small-molecule survivin suppressant, exhibits anti-tumor activities in vitro, in vivo and in clinical trials. However, the mechanism of YM155 action remains unclear. In this study, YM155 was administered to a panel of cell lines and the effects of YM155 on Bcl-2 family members were analyzed. Our results show that YM155 strikingly downregulates Mcl-1 in a broad spectrum of cancer cell lines and that the Mcl-1 modulation occurs at the transcriptional level, independently of survivin modulation or caspase activity. Furthermore, analysis of the contribution of Mcl-1 or survivin downregulation to YM155-induced cell death in vitro showed that knockdown of Mcl-1 sensitizes cells to YM155-induced cytotoxicity. Finally, our data demonstrate that downregulation of Mcl-1 by YM155 synergistically lowers the threshold of Bcl-2 family member inhibitor ABT-263-induced cell death. Our findings reveal a novel mechanism by which survivin-independent Mcl-1 suppression plays a critical role in YM155-mediated anti-tumor activities. YM155 treatment in combination with ABT-263 thus affords a new strategy for cancer treatment.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical Pharmacology - Volume 82, Issue 9, 1 November 2011, Pages 1066-1072
Journal: Biochemical Pharmacology - Volume 82, Issue 9, 1 November 2011, Pages 1066-1072
نویسندگان
Haikuo Tang, Huanjie Shao, Chunrong Yu, Jinsong Hou,