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https://ir.csmu.edu.tw:8080/ir/handle/310902500/15976
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Title: | Honokiol inhibits gastric tumourigenesis by activation of 15-lipoxygenase-1 and consequent inhibition of peroxisome proliferator-activated receptor-γ and COX-2-dependent signals |
Authors: | admin, admin Liu, Shing Hwa;Shen, Chin Chang;Yi, Yu Chiao;Tsai, Jaw Ji;Wang, Chih Chien;Chueh, Ju Ting;Lin, Keh Liang;Lee, Tso Ching;Pan, Hung Chuan;Sheu, Meei Ling |
Contributors: | 中山醫學大學 |
Keywords: | gastric tumourigenesis;honokiol;calpain;15-LOX-1;PPAR-γ;COX-2 |
Date: | 2010 |
Issue Date: | 2016-09-07T06:50:14Z (UTC)
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ISSN: | 0007-1188 |
Abstract: | Background and purpose:
Peroxisome proliferator-activated receptor-γ (PPAR-γ), COX-2 and 15-lipoxygenase (LOX)-1 have been shown to be involved in tumour growth. However, the roles of PPAR-γ, 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-γ 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-γ 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-γ and COX-2 proteins were highly expressed in gastric cancer cells. Inhibitors, or siRNA for COX-2 or PPAR-γ, significantly decreased cell viability. Honokiol markedly inhibited PPAR-γ 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-γ 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-γ and COX-2 pathway by honokiol may be a promising therapeutic strategy for gastric cancer. |
URI: | http://dx.doi.org/10.1111/j.1476-5381.2010.00804.x https://ir.csmu.edu.tw:8080/ir/handle/310902500/15976 |
Relation: | Br J Pharmacol. 2010 Aug; 160(8): 1963–1972. |
Appears in Collections: | [醫學檢驗暨生物技術學系暨碩士班] 期刊論文
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