Curcumin Reactivates Silenced Tumor Suppressor Gene RAR beta by Reducing DNA Methylation

摘要

Reactivation of tumor suppressor genes by nontoxic bioactive food component represents a promising strategy for cancer chemoprevention. Retinoic acid receptor (RAR), one member of the RAR receptor family, is considered as a tumor suppressor. Reduced expression of RAR has been reported in lung cancer and other solid tumors. DNA hypermethylation of the promoter region of RAR 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 RAR expression at the mRNA and protein levels in tested cancer cells. Additionally, curcumin decreased RAR 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, RAR 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 RAR. Copyright (c) 2015 John Wiley & Sons, Ltd.