Heimer, Sina and Knoll, Gertrud and Schulze-Osthoff, Klaus and Ehrenschwender, Martin (2019) Raptinal bypasses BAX, BAK, and BOK for mitochondrial outer membrane permeabilization and intrinsic apoptosis. CELL DEATH & DISEASE, 10: 556. ISSN 2041-4889,
Full text not available from this repository. (Request a copy)Abstract
Most antineoplastic chemotherapies eliminate cancer cells through activation of the mitochondria-controlled intrinsic apoptotic pathway. Therein, BAX, BAK, and/or BOK function as the essential pore-forming executioners of mitochondrial outer membrane permeabilization (MOMP). The activation threshold of BAX and BAK also correlates inversely with the required strength of an apoptotic stimulus to induce MOMP and thereby effectively determines a cell's readiness to undergo apoptosis. Consequently, the 'gatekeepers' BAX and BAK emerged as therapeutic targets, but functional or genetic loss renders BAX/BAK-targeting strategies prone to fail. Here, we show that the small molecule Raptinal overcomes this limitation by triggering cytochrome c release in a BAX/BAK/BOK-independent manner. Raptinal exerts a dual cytotoxic effect on cancer cells by rapid activation of the intrinsic apoptotic pathway and simultaneous shutdown of mitochondrial function. Together with its efficacy to eliminate cancer cells in vivo, Raptinal could be useful in difficult-to-treat cancer entities harboring defects in the intrinsic apoptosis pathway.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | SMALL-MOLECULE; BCL-2 PROTEIN; CYTOCHROME-C; ACTIVATION; DYSFUNCTION; INHIBITOR; CHANNELS; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene Medicine > Lehrstuhl für Mund-, Kiefer- und Gesichtschirurgie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 02 Apr 2020 12:17 |
| Last Modified: | 02 Apr 2020 12:17 |
| URI: | https://pred.uni-regensburg.de/id/eprint/26617 |
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