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標題: Destabilization of CARP mRNAs by Aloe-Emodin Contributes to Caspase-8-Mediated p53-Independent Apoptosis of Human Carcinoma Cells
作者: 蘇鴻麟
Lin, M.L.
Lu, Y.C.
Su, H.L.
Lin, H.T.
Lee, C.C.
Kang, S.E.
Lai, T.C.
Chung, J.G.
Chen, S.S.
Project: Journal of Cellular Biochemistry
期刊/報告no:: Journal of Cellular Biochemistry, Volume 112, Issue 4, Page(s) 1176-1191.
Using short hairpin RNA against p53, transient ectopic expression of wild-type p53 or mutant p53 (R248W or R175H), and a p53- and p21-dependent luciferase reporter assay, we demonstrated that growth arrest and apoptosis of FaDu (human pharyngeal squamous cell carcinoma), Hep3B (hepatoma), and MG-63 (osteosarcoma) cells induced by aloe-emodin (AE) are p53-independent. Co-immunoprecipitation and small interfering RNA (siRNA) studies demonstrated that AE caused S-phase cell cycle arrest by inducing the formation of cyclin A-Cdk2-p21 complexes through extracellular signal-regulated kinase (ERK) activation. Ectopic expression of Bcl-X(L) and siRNA-mediated Bax attenuation significantly inhibited apoptosis induced by AE. Cyclosporin A or the caspase-8 inhibitor Z-IETD-FMK blocked AE-induced loss of mitochondrial membrane potential and prevented increases in reactive oxygen species and Ca(++). Z-IETD-FMK inhibited AE-induced apoptosis, Bax expression, Bid cleavage, translocation of tBid to mitochondria, ERK phosphorylation, caspase-9 activation, and the release of cytochrome c, apoptosis-inducing factor (AIF), and endonuclease G from mitochondria. The stability of the mRNAs encoding caspase-8 and 10-associated RING proteins (CARPs) 1 and 2 was affected by AE, whereas CARP1 or 2 overexpression inhibited caspase-8 activation and - apoptosis induced by AE. Collectively, our data indicate AE induces caspase-8-mediated activation of mitochondrial death pathways by decreasing the stability of CARP mRNAs in a p53-independent manner. J. Cell. Biochem. 112: 1176-1191, 2011. (C) 2011 Wiley-Liss, Inc.
ISSN: 0730-2312
DOI: 10.1002/jcb.23031
Appears in Collections:生命科學系所

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