Combretastatin A-4 induces p53 mitochondrial-relocalisation independent-apoptosis in non-small lung cancer cells.

作者: Gina Marcela Méndez-Callejas , Stefano Leone , Caterina Tanzarella , Antonio Antoccia

DOI: 10.1002/CBIN.10199

关键词:

摘要: Combretastatin A-4 (CA-4) is one of the most effective agents used in chemotherapy. Nevertheless, contribution p53 and Bim proteins CA-4-induced apoptosis non-small lung cancer cells (NSCLC) remains unresolved, specifically on involving mitochondrial pathway activation by a transcription-independent mechanism. In this context, p53-null H1299 wt-p53 H460 NSCLC cells, absence presence pifithrin-µ (PFTµ), an inhibitor mitochondrial-translocation, were treated with CA-4 different cellular endpoints analysed. contrast to previous observations failed apoptotic response thus indicating involvement cell death induced drug. We found that led re-localisation cells; particular, was released from microtubular network accumulated at mitochondria where it interacts protein other Bcl-2 (B-cell leukaemia-2) family, leading cytochrome c release, alteration membrane polarisation, cycle arrest G2/M-phase, death. Interestingly, cytosolic accumulation strictly dependent status. The extent not reduced after combined treatment PFTµ CA-4. Overall, data support model NSCLC, for which expression essential, but its function, linked p53-transcription independent pathway, negligible.

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