NDLI: The oncolytic peptide LTX-315 kills cancer cells through Bax/Bak-regulated mitochondrial membrane permeabilization.

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The oncolytic peptide LTX-315 kills cancer cells through Bax/Bak-regulated mitochondrial membrane permeabilization.

Content Provider	Europe PMC
Author	Zhou, Heng Forveille, Sabrina Sauvat, Allan Sica, Valentina Izzo, Valentina Durand, Sylvère Müller, Kevin Liu, Peng Zitvogel, Laurence Rekdal, Øystein Kepp, Oliver Kroemer, Guido
Copyright Year	2015
Abstract	LTX-315 has been developed as an amphipathic cationic peptide that kills cancer cells. Here, we investigated the putative involvement of mitochondria in the cytotoxic action of LTX-315. Subcellular fractionation of LTX-315-treated cells, followed by mass spectrometric quantification, revealed that the agent was enriched in mitochondria. LTX-315 caused an immediate arrest of mitochondrial respiration without any major uncoupling effect. Accordingly, LTX-315 disrupted the mitochondrial network, dissipated the mitochondrial inner transmembrane potential, and caused the release of mitochondrial intermembrane proteins into the cytosol. LTX-315 was relatively inefficient in stimulating mitophagy. Cells lacking the two pro-apoptotic multidomain proteins from the BCL-2 family, BAX and BAK, were less susceptible to LTX-315-mediated killing. Moreover, cells engineered to lose their mitochondria (by transfection with Parkin combined with treatment with a protonophore causing mitophagy) were relatively resistant against LTX-315, underscoring the importance of this organelle for LTX-315-mediated cytotoxicity. Altogether, these results support the notion that LTX-315 kills cancer cells by virtue of its capacity to permeabilize mitochondrial membranes.
Journal	Oncotarget
Volume Number	6
PubMed Central reference number	PMC4694939
Issue Number	29
PubMed reference number	26378049
e-ISSN	19492553
DOI	10.18632/oncotarget.5613
Language	English
Publisher	Impact Journals LLC
Publisher Date	2015-09-01
Access Restriction	Open
Rights License	This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Copyright: © 2015 Zhou et al.
Subject Keyword	LTX-315 necrosis mitochondrial membrane permeabilization cancer mitophagy
Content Type	Text
Resource Type	Article
Subject	Oncology

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