MAPK inhibitors and pifithrin-alpha block cinnamaldehyde-induced apoptosis in human PLC/PRF/5 cells

doi:10.1016/j.fct.2007.05.032

Chia Nan University of Pharmacy & Science Institutional Repository > 藥理學院 > 保健營養系(所) > 期刊論文 > Item 310902800/22222

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標題:	MAPK inhibitors and pifithrin-alpha block cinnamaldehyde-induced apoptosis in human PLC/PRF/5 cells
作者:	Shu-Jing Wu Lean-Teik Ng
貢獻者:	營養與保健科技研究所
關鍵字:	Cinnamaldehyde PFTα MAPK inhibitors Apoptosis PLC/PRF/5 cells
日期:	2007-12
上傳時間:	2010-01-15 11:13:26 (UTC+8)
摘要:	Cinnamaldehyde (Cin) has been shown to be effective in inducing apoptotic cell death in a number of human cancer cells. The aim of this study was to investigate the effect of pifithrin-alpha (PFTα; a specific p53 inhibitor) and mitogen-activated protein kinases (MAPKs) inhibitors [namely SP600125 (a specific JNK inhibitor), SB203580 (a specific p38 inhibitor) and PD98059 (a specific ERK inhibitor)] on apoptotic signaling transduction mechanism induced by Cin in human hepatoma PLC/PRF/5 (CD95-negative) cells. Using XTT assay, Cin exhibited a powerful cytotoxic effect and apoptotic induction in PLC/PRF/5 cells. Apoptosis was elicited when cells were treated with 1 μM Cin as characterized by morphological changes and the appearance of phosphatidylserine on the outer surface of the plasma membrane. Cin down-regulated the expression of Bcl-XL, up-regulated mutant p53 and Bax proteins and promoted caspase-3 to active forms, as well as cleaving poly (ADP-ribose) polymerase (PARP) in a time-dependent pattern. This could be supported by the activation and phosphorylation of MAPKs, including JNK, ERK and p38 kinases. Pre-incubation with PFTα and specific MAPK inhibitors significantly diminished the effect of Cin-induced apoptosis. The activities of anti-apoptotic (Bcl-XL) and pro-apoptotic (Bax) proteins were remarkably affected by PFTα and PD98059 pre-treatment. PFTα effectively blocked PARP cleavage in cells treated with Cin, and also markedly prevented the phosphorylation of JNK, p38 and ERK proteins. These results suggest that p53 induction and MAPK signaling pathways are required for Cin-mediated apoptosis in PLC/PRF/5 cells.
關聯:	Food and Chemical Toxicology 45(12)： p.2446-2453
显示于类别:	[保健營養系(所) ] 期刊論文

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