title: Reactivation of RASSF1A in breast cancer cells by curcumin.
abstract: Reactivation of tumor suppressor genes (TSGs) involved in carcinogenesis by nontoxic bioactive food component represents a promising strategy for cancer chemoprevention. Recently, curcumin has been demonstrated to inhibit a bacterial DNA methyltransferase (M. Sss I) activity, induce global DNA hypomethylation in leukemia cells, and reactivate several hypermethylation silenced genes in lung and prostate cancer cells. Herein, we demonstrated that curcumin can enhance the mRNA and protein levels of ras-association domain family protein 1A (RASSF1A), 1 hypermethylation-silenced TSG, and decrease its promoter methylation in breast cancer cells. Mechanistic study demonstrated that curcumin can decrease DNA methylation activity of nuclear extract and downregulate the mRNA and protein levels of DNMT1 in MCF-7 cells, which may be associated with curcumin-induced disruption of NF-κB/Sp1 complex bound to the promoter region of DNMT1. Altogether, this study reveals a novel molecular mechanism of curcumin as a chemo-preventive agent for breast cancer through hypomethylation reactivation of RASSF1A.
authors.affiliation: College of Pharmacy, Ohio State University, Columbus, Ohio 43210, USA.
authors.forename: Liping
authors.initials: L
authors.lastname: Du
authors.forename: Zhiliang
authors.initials: Z
authors.lastname: Xie
authors.forename: Lai-chu
authors.initials: LC
authors.lastname: Wu
authors.forename: Ming
authors.initials: M
authors.lastname: Chiu
authors.forename: Jiayuh
authors.initials: J
authors.lastname: Lin
authors.forename: Kenneth K
authors.initials: KK
authors.lastname: Chan
authors.forename: Shujun
authors.initials: S
authors.lastname: Liu
authors.forename: Zhongfa
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000737:chemistry / Q000378:metabolism / Q000517:prevention & control*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D019175:DNA Methylation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D008819:Mice, Nude; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D012097:Repressor Proteins / Q000032:analysis / Q000235:genetics; D015533:Transcriptional Activation / Q000187:drug effects*; D025521:Tumor Suppressor Proteins / Q000032:analysis / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
chemical_list: C411744:DMAP1 protein, human; C411762:RASSF1 protein, human; D012333:RNA, Messenger; D012097:Repressor Proteins; D025521:Tumor Suppressor Proteins; D003474:Curcumin