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Indexed by:期刊论文

Date of Publication:2013-09-01

Journal:BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY

Included Journals:SCIE、PubMed、Scopus

Volume:113

Issue:3

Page Number:145-151

ISSN No.:1742-7835

Abstract:Small molecule S1 is a pan-BH3 mimetic that can bind antiapoptotic Bcl-2, Bcl-xL and Mcl-1 proteins. Herein, different Bcl-2 member expression cancer cell lines (NCI-H345, MCF-7, SMMC-7721 and Hela) and cells deficient in Bax and/or Bak by shRNA were used to unravel the cascade of events by which S1 promotes apoptosis compared with Bcl-2/Bcl-xL inhibitor ABT-737. We identified that S1 exhibited broader antitumour spectrum than ABT-737 through disruption of more Bcl-2 interactions including Mcl-1/Bak interaction. Moreover, the individual and combined roles of Bax and Bak in S1-induced apoptosis were revealed. Our results showed that S1 induced a Bak-mediated apoptosis. Bak played a predominant role in either S1 or ABT-737-induced apoptosis through the cooperation with Bax on the formation of large oligomers on mitochondrial membrane.