Reactivation of RASSF1A in breast cancer cells by curcumin

Liping Du, Zhiliang Xie, Lai Chu Wu, Ming Chiu, Jiayuh Lin, Kenneth K. Chan, Shujun Liu, Zhongfa Liu

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

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 molecularmechanism of curcumin as a chemo-preventive agent for breast cancer through hypomethylation reactivation of RASSF1A.

Original languageEnglish (US)
Pages (from-to)1228-1235
Number of pages8
JournalNutrition and Cancer
Volume64
Issue number8
DOIs
StatePublished - 2012

Bibliographical note

Funding Information:
This work was supported by National Institute of Health (NIH) grants [R21 CA135478] (Zhongfa Liu), and Biomedical Mass Spectrometric Laboratory (Kenneth K. Chan and Zhongfa Liu) at the Ohio State University.

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