| First Author | Valero JG | Year | 2011 |
| Journal | J Cell Sci | Volume | 124 |
| Issue | Pt 4 | Pages | 556-64 |
| PubMed ID | 21245196 | Mgi Jnum | J:182880 |
| Mgi Id | MGI:5317042 | Doi | 10.1242/jcs.076745 |
| Citation | Valero JG, et al. (2011) Bax-derived membrane-active peptides act as potent and direct inducers of apoptosis in cancer cells. J Cell Sci 124(Pt 4):556-64 |
| abstractText | 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. |
