Proapoptotic Action of p53-Tom5 in p53-Resistant A549 Human Non-small Cell Lung Cancer Cells through Direct Mitochondrial Dysfunction

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Transcription-dependent apoptosis triggered by p53 hardly occurs in alternative reading frame (ARF)-null cancer cells. Loss of ARF leads to hyperactivation of murine double minute 2 (MDM2), resulting in the degradation of p53. In the present study, A549 (ARF-null) human non-small lung cancer cells were transfected with a plasmid DNA encoding human wild-type p53 and the mitochondrial transmembrane domain of Tom5 (p53-Tom5) for delivering p53 to mitochondria. As a result, p53-Tom5 exclusively localized at mitochondria in A549 cells and suppressed the proliferation of them, whereas wild-type p53 did not. In addition, mitochondrial dysfunction and release of cytochrome c were induced by p53-Tom5 in A549 cells. These data suggest that p53-Tom5 suppressed the proliferation of A549 cells through direct mitochondrial dysfunction.
公益社団法人　日本薬学会の論文