title: Curcumin Suppresses MAPK Pathways to Reverse Tobacco Smoke-induced Gastric Epithelial-Mesenchymal Transition in Mice.
abstract: 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.
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
authors.forename: Zhaofeng
authors.initials: Z
authors.lastname: Liang
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Wu
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xie
authors.affiliation: Department of Surgery, Second Affiliated Hospital of Anhui Medical University, Hefei, 230032, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Geng
authors.affiliation: Department of Surgery, Second Affiliated Hospital of Anhui Medical University, Hefei, 230032, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.|The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
authors.forename: Chunfeng
authors.initials: C
authors.lastname: Xie
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.|The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
authors.forename: Jieshu
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.|The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Geng
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.|The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
authors.forename: Xiaoting
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
authors.forename: Mingming
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
authors.forename: Jianyun
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
authors.forename: Cong
authors.initials: C
authors.lastname: Huang
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Ma
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.|The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
authors.forename: Caiyun
authors.initials: C
authors.lastname: Zhong
authors.affiliation: Department of Clinical Nutrition, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Han
mesh_terms: D000818:Animals; D015820:Cadherins / Q000378:metabolism; D003474:Curcumin / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation; D012906:Smoke; D018808:Transcription Factor AP-1 / Q000378:metabolism
chemical_list: D015820:Cadherins; D004791:Enzyme Inhibitors; D012906:Smoke; D018808:Transcription Factor AP-1; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D003474:Curcumin
keywords: MAPK; curcumin; epithelial-mesenchymal transition; gastric cancer; tobacco smoke