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Bax-derived membrane-active peptides act as potent and direct inducers of apoptosis in cancer cells.: A membrane-active Bax peptide has antitumor activity

Abstract : Although many cancer cells are primed for apoptosis, they usually develop resistance to cell death at several levels. Permeabilization of the outer mitochondrial membrane, which is mediated by proapoptotic Bcl-2 family members such as Bax, is considered as a point of no return for initiating apoptotic cell death. This crucial role has placed Bcl-2 family proteins as recurrent targets for anticancer drug development. Here, we propose and demonstrate a new concept based on minimal active versions of Bax to induce cell death independently of endogenous Bcl-2 proteins. We show that membrane-active segments of Bax can directly induce the release of mitochondria-residing apoptogenic factors and commit tumor cells promptly and irreversibly to caspase-dependent apoptosis. On this basis, we designed a peptide encompassing part of the Bax pore-forming domain, which can target mitochondria, induce cytochrome c release and trigger caspase-dependent apoptosis. Moreover, this Bax-derived 'poropeptide' produced effective tumor regression after peritumoral injection in a nude mouse xenograft model. Thus, peptides derived from proteins that form pores in the mitochondrial outer membrane represent novel templates for anticancer agents.
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https://www.hal.inserm.fr/inserm-00559538
Contributor : Amandine Hurbin <>
Submitted on : Thursday, January 19, 2012 - 8:48:44 AM
Last modification on : Monday, November 23, 2020 - 1:18:03 PM
Long-term archiving on: : Friday, April 20, 2012 - 2:20:08 AM

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Juan Garcia Valero, Lucie Sancey, Jérôme Kucharczak, Yannis Guillemin, Diana Gimenez, et al.. Bax-derived membrane-active peptides act as potent and direct inducers of apoptosis in cancer cells.: A membrane-active Bax peptide has antitumor activity. Journal of Cell Science, Company of Biologists, 2011, 124 (Pt 4), pp.556-64. ⟨10.1242/jcs.076745⟩. ⟨inserm-00559538⟩

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