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标题：Proapoptotic Action of p53-Tom5 in p53-Resistant A549 Human Non-small Cell Lung Cancer Cells through Direct Mitochondrial Dysfunction
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作者：Takuya Umemoto ; Tomohiro Asai ; Koji Hirashima 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2011
卷号：34
期号：4
页码：551-554
DOI：10.1248/bpb.34.551
出版社：The Pharmaceutical Society of Japan
摘要：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.
关键词：p53-Tom5;gene therapy;mitochondria;alternative reading frame;gene delivery system