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.
journal_name
Biol Chemjournal_title
Biological chemistryauthors
Henz K,Al-Zebeeby A,Basoglu M,Fulda S,Cohen GM,Varadarajan S,Vogler Mdoi
10.1515/hsz-2018-0233subject
Has Abstractpub_date
2019-01-28 00:00:00pages
181-185issue
2eissn
1431-6730issn
1437-4315pii
/j/bchm.just-accepted/hsz-2018-0233/hsz-2018-0233.journal_volume
400pub_type
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