Honokiol inhibits gastric tumourigenesis by activation of 15-lipoxygenase-1 and consequent inhibition of peroxisome proliferator-activated receptor-gamma and COX-2-dependent signals.

British Journal of Pharmacology
Shing Hwa LiuMeei Ling Sheu

Abstract

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. 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. 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 metabol...Continue Reading

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Citations

Nov 1, 2011·Cancer Metastasis Reviews·Sun Il LeeImad Shureiqi
Sep 11, 2012·Prostaglandins & Other Lipid Mediators·Xiangsheng Zuo, Imad Shureiqi
Jul 28, 2016·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Vincent Kam-Wai WongElaine Lai-Han Leung
Jun 23, 2015·Critical Reviews in Oncology/hematology·Ning WangAijun Zhu
Feb 14, 2013·Genes, Chromosomes & Cancer·Sarah E KleinsteinCornelia M Ulrich
Apr 21, 2016·Journal of the Chinese Medical Association : JCMA·Hsiao-Chi ChenChin-Wen Chi
Dec 28, 2019·Cancers·Chon Phin OngWei Hsum Yap
Jun 10, 2011·Free Radical Research·Bokyung SungBharat B Aggarwal
Aug 28, 2014·Cancer Prevention Research·Faya M MillimounoXiaomeng Li

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