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Curcumin Reactivates Silenced Tumor Suppressor Gene RARβ by Reducing DNA Methylation

Apei Jiang1,2, Xuemin Wang2, Xiaoyun Shan2

  • 1College of Basic Medical Science, Zhejiang Chinese Medical School, Hangzhou, Zhejiang, 310053, China.

Phytotherapy Research : PTR
|May 19, 2015
PubMed

Insights

Curcumin, a bioactive food component, reactivates the tumor suppressor gene Retinoic acid receptor beta (RARβ) in lung cancer cells. This novel mechanism involves reducing DNA methylation and inhibiting DNMT3b, offering a promising strategy for cancer chemoprevention.

Area of Science:

  • Oncology
  • Molecular Biology
  • Nutritional Science

Background:

  • Retinoic acid receptor beta (RARβ) acts as a tumor suppressor, with its reduced expression linked to lung cancer.
  • DNA hypermethylation of the RARβ promoter is a key mechanism for its silencing in tumors.
  • Curcumin is being investigated for its potential as a DNA methyltransferase inhibitor.

Purpose of the Study:

  • To investigate the effect of curcumin on RARβ expression in cancer cells.
  • To explore the molecular mechanisms underlying curcumin's action, including DNA methylation and DNMT3b.
  • To evaluate the efficacy of curcumin as a chemopreventive agent in a lung cancer mouse model.

Main Methods:

  • Assessing RARβ mRNA and protein levels after curcumin treatment in cancer cell lines.
  • Analyzing RARβ promoter methylation and DNMT3b mRNA levels.
  • Conducting in vivo studies using a lung cancer xenograft mouse model to assess tumor growth and RARβ/DNMT3b expression.

Main Results:

  • Curcumin significantly increased RARβ expression at both mRNA and protein levels.
  • Curcumin treatment reduced RARβ promoter methylation in lung cancer cells.
  • Curcumin downregulated DNMT3b mRNA levels in vitro and in vivo, and repressed tumor growth in mice.

Conclusions:

  • Curcumin reactivates the tumor suppressor RARβ in lung cancer cells.
  • This reactivation is mediated by the inhibition of DNA methyltransferase 3 beta (DNMT3b), leading to decreased promoter methylation.
  • Curcumin demonstrates potential as a chemopreventive agent for lung cancer through this novel molecular pathway.
Keywords:
DNA methylationRARβcurcumin

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