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Curcumin Suppresses MAPK Pathways to Reverse Tobacco Smoke‐induced Gastric Epithelial–Mesenchymal Transition in Mice
Author(s) -
Liang Zhaofeng,
Wu Rui,
Xie Wei,
Geng Hao,
Zhao Li,
Xie Chunfeng,
Wu Jieshu,
Geng Shanshan,
Li Xiaoting,
Zhu Mingming,
Zhu Weiwei,
Zhu Jianyun,
Huang Cong,
Ma Xiao,
Zhong Caiyun,
Han Hongyu
Publication year - 2015
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.5398
Subject(s) - mapk/erk pathway , curcumin , epithelial–mesenchymal transition , kinase , protein kinase a , p38 mitogen activated protein kinases , cancer research , activator (genetics) , carcinogenesis , signal transduction , chemistry , cancer , biology , microbiology and biotechnology , medicine , pharmacology , metastasis , biochemistry , receptor
Tobacco smoke (TS) has been shown to cause gastric cancer. Epithelial–mesenchymal transition (EMT) is a crucial pathophysiological process in cancer development. Mitogen‐activated protein kinase (MAPK) pathways play central roles in tumorigenesis including EMT process. Curcumin is a promising chemopreventive agent for several types of cancers. In the present study, we investigated the effects of TS on MAPK pathway activation and EMT alterations in the stomach of mice, and the preventive effect of curcumin was further examined. Results showed that exposure of mice to TS for 12 weeks resulted in activation of extracellular regulated protein kinases 1 and 2 (ERK1/2), the Jun N‐terminal kinase (JNK), p38, and ERK5 MAPK pathways as well as activator protein 1 (AP‐1) proteins in stomach. TS reduced the mRNA and protein expression levels of the epithelial markers E‐cadherin and ZO‐1, while the mRNA and protein expression levels of the mesenchymal markers vimentin and N‐cadherin were increased. Treatment of curcumin effectively abrogated TS‐triggered gastric activation of ERK1/2 and JNK MAPK pathways, AP‐1 proteins, and EMT alterations. These results suggest for the first time the protective effects of curcumin in long‐term TS exposure‐induced gastric MAPK activation and EMT, thus providing new insights into the pathogenesis and chemoprevention of TS‐associated gastric cancer. Copyright © 2015 John Wiley & Sons, Ltd.