title: Curcumin Reactivates Silenced Tumor Suppressor Gene RARβ by Reducing DNA Methylation.
abstract: Reactivation of tumor suppressor genes by nontoxic bioactive food component represents a promising strategy for cancer chemoprevention. Retinoic acid receptor β (RARβ), one member of the RAR receptor family, is considered as a tumor suppressor. Reduced expression of RARβ has been reported in lung cancer and other solid tumors. DNA hypermethylation of the promoter region of RARβ is a major mechanism for its silencing in tumors. Recently, curcumin has been considered as a potential DNA methyltransferase inhibitor. Herein, we demonstrated that curcumin significantly elevate RARβ expression at the mRNA and protein levels in tested cancer cells. Additionally, curcumin decreased RARβ promoter methylation in lung cancer A549 and H460 cells. Mechanistic study demonstrated that curcumin was able to downregulate the mRNA levels of DNMT3b. In a lung cancer xenograft node mice model, curcumin exhibited protective effect against weight loss because of tumor burden. Tumor growth was strongly repressed by curcumin treatment. As the results from in vitro, RARβ mRNA were increased and DNMT3b mRNA were decreased by curcumin treatment compared with the mice in control group. Altogether, this study reveals a novel molecular mechanism of curcumin as a chemo-preventive agent for lung cancer through reactivation of RARβ.
authors.affiliation: College of Basic Medical Science, Zhejiang Chinese Medical School, Hangzhou, Zhejiang, 310053, China.|Department of Nutrition and Food Hygiene, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, 211166, China.
authors.forename: Apei
authors.initials: A
authors.lastname: Jiang
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, 211166, China.
authors.forename: Xuemin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, 211166, China.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Shan
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, 211166, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, 211166, China.
authors.forename: Pengqi
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, 211166, China.
authors.forename: Pan
authors.initials: P
authors.lastname: Jiang
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, 211166, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Feng
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism; D019175:DNA Methylation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D016147:Genes, Tumor Suppressor; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D023041:Xenograft Model Antitumor Assays; D000097584:DNA Methyltransferase 3B
chemical_list: D003474:Curcumin; D004248:DNA (Cytosine-5-)-Methyltransferases; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D000097584:DNA Methyltransferase 3B; C082925:retinoic acid receptor beta
keywords: DNA methylation; RARβ; curcumin