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.

中文翻译：

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Bcl-xL介导的细胞凋亡的化学，物理和生物学诱因

pan-Bcl-2或Bcl-xL特异性抑制剂过早杀死病毒感染的细胞或RNA / DNA转染的细胞的证据为进一步研究这些凋亡诱导物提供了依据。在这里，我们显示Bcl-xL特异试剂A-1155463与DNA破坏剂4-硝基喹啉-1-氧化物（4NQO）结合会过早地杀死不同来源的细胞和小round虫（C. elegans）。4NQO-A-1155463组合的协同效应是p53依赖性的，与Bcl-xL中Bad和Bax的释放有关，这触发了线粒体外膜通透性（MOMP）。Bcl-xL特异性抑制剂与某些抗癌化合物或物理损伤的组合也可以杀死细胞。总的来说，我们的结果表明，生物学，化学和物理因素触发了保守的Bcl-xL介导的凋亡途径。