Chemical, physical and biological triggers of Bcl-xL-mediated apoptosis
Albert F Arutyunyan,
Olga Yu Susova,
Alexei L Zhuze,
Joachim M. Gerhold,
Evandro F Fang,
Denis E. Kainov
Posted 13 Jan 2020
bioRxiv DOI: 10.1101/2020.01.13.904714 (published DOI: 10.3390/cancers12061694)
Posted 13 Jan 2020
The evidence that pan-Bcl-2 or Bcl-xL-specific inhibitors prematurely kill virus-infected or RNA/DNA-transfected cells provides rationale for investigating these apoptotic inducers further. Here, we show that Bcl-xL-specific agent A-1155463 prematurely kills cells of different origins and the small roundworms (C. elegans), when combined with DNA-damaging agent 4-nitroquinoline-1-oxide (4NQO). The synergistic effect of 4NQO-A-1155463 combination was p53-dependent, was associated with the release of Bad and Bax from Bcl-xL, which triggered mitochondrial outer membrane permeabilization (MOMP). Combinations of Bcl-xL-specific inhibitors with certain anticancer compounds or physical insults also killed cells. Collectively, our results suggest that biological, chemical and physical factors trigger evolutionary conserved Bcl-xL-mediated apoptotic pathway. ### Competing Interest Statement The authors have declared no competing interest.
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