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Biol Chem. 2019 Jan 28;400(2):181-185. doi: 10.1515/hsz-2018-0233.

Selective BH3-mimetics targeting BCL-2, BCL-XL or MCL-1 induce severe mitochondrial perturbations.

Author information

1
Institute for Experimental Cancer Research in Pediatrics, Goethe-University Frankfurt, Komturstr. 3a, D-60528 Frankfurt/Main, Germany.
2
Department of Molecular and Clinical Cancer Medicine and Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
3
Department of Biology, Goethe-University Frankfurt, Frankfurt, Germany.
4
German Cancer Consortium (DKTK), Heidelberg, Germany.
5
German Cancer Research Center (DKFZ), Heidelberg, Germany.

Abstract

Induction of apoptosis by selective BH3-mimetics is currently investigated as a novel strategy for cancer treatment. Here, we report that selective BH3-mimetics induce apoptosis in a variety of hematological malignancies. Apoptosis is accompanied by severe mitochondrial toxicities upstream of caspase activation. Specifically, the selective BH3-mimetics ABT-199, A-1331852 and S63845, which target BCL-2, BCL-XL and MCL-1, respectively, induce comparable ultrastructural changes including mitochondrial swelling, a decrease of mitochondrial matrix density and severe loss of cristae structure. These shared effects on mitochondrial morphology indicate a similar function of these anti-apoptotic BCL-2 proteins in maintaining mitochondrial integrity and function.

KEYWORDS:

BCL-2 proteins; BH3-mimetics; apoptosis; mitochondria

PMID:
29924730
DOI:
10.1515/hsz-2018-0233
[Indexed for MEDLINE]

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