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標題: Honokiol inhibits gastric tumourigenesis by activation of 15-lipoxygenase-1 and consequent inhibition of peroxisome proliferator-activated receptor-gamma and COX-2-dependent signals
作者: Liu, S.H.
Shen, C.C.
Yi, Y.C.
Tsai, J.J.
Wang, C.C.
Chueh, J.T.
Lin, K.L.
Lee, T.C.
Pan, H.C.
Sheu, M.L.
關鍵字: gastric tumourigenesis;honokiol;calpain;15-LOX-1;PPAR-gamma;COX-2;colorectal-cancer cells;ppar-gamma;cox-2 inhibitors;cyclooxygenase-2;inhibitor;induced apoptosis;in-vivo;angiogenesis;expression;growth;carcinogenesis
Project: British Journal of Pharmacology
期刊/報告no:: British Journal of Pharmacology, Volume 160, Issue 8, Page(s) 1963-1972.
Background and purpose: Peroxisome proliferator-activated receptor-gamma (PPAR-gamma), COX-2 and 15-lipoxygenase (LOX)-1 have been shown to be involved in tumour growth. However, the roles of PPAR-gamma, COX-2 or 15-LOX-1 in gastric tumourigenesis remain unclear. Here, we investigate the role of 15-LOX-1 induction by honokiol, a small-molecular weight natural product, in PPAR-gamma and COX-2 signalling during gastric tumourigenesis. Experimental approach: Human gastric cancer cell lines (AGS, MKN45, N87 and SCM-1) were cultured with or without honokiol. Gene and protein expressions were analysed by RT-PCR and Western blotting respectively. Small interfering RNAs (siRNAs) for COX-2, PPAR-gamma and 15-LOX-1 were used to interfere with the expressions of these genes. A xenograft gastric tumour model in mouse was used for in vivo study. Key results: PPAR-gamma and COX-2 proteins were highly expressed in gastric cancer cells. Inhibitors, or siRNA for COX-2 or PPAR-gamma, significantly decreased cell viability. Honokiol markedly inhibited PPAR-gamma and COX-2 expressions in gastric cancer cells and tumours of xenograft mice, and induced apoptosis and cell death. Honokiol markedly activated cellular 15-LOX-1 expression and 13-S-hydroxyoctadecadienoic acid (a primary product of 15-LOX-1 metabolism of linoleic acid) production. 15-LOX-1 siRNA could reverse the honokiol-induced down-regulation of PPAR-gamma and COX-2, and cell apoptosis. 15-LOX-1 was markedly induced in tumours of xenograft mice treated with honokiol. Conclusions and implications: These findings suggest that induction of 15-LOX-1-mediated down-regulation of a PPAR-gamma and COX-2 pathway by honokiol may be a promising therapeutic strategy for gastric cancer.
ISSN: 0007-1188
DOI: 10.1111/j.1476-5381.2010.00804.x
Appears in Collections:生物醫學研究所

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