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Reactivation of RASSF1A in breast cancer cells by curcumin

Liping Du1, Zhiliang Xie, Lai-chu Wu

  • 1College of Pharmacy, Ohio State University, Columbus, Ohio 43210, USA.

Nutrition and Cancer
|November 14, 2012
PubMed

Insights

Curcumin, a bioactive food component, reactivates the RASSF1A tumor suppressor gene in breast cancer cells by reducing DNA methylation. This study reveals a novel mechanism for curcumin

Area of Science:

  • Oncology
  • Molecular Biology
  • Nutritional Science

Background:

  • Nontoxic bioactive food components can reactivate tumor suppressor genes (TSGs) for cancer chemoprevention.
  • Curcumin has shown potential in inhibiting DNA methyltransferase activity and reactivating silenced genes in various cancer cells.

Purpose of the Study:

  • To investigate curcumin's effect on the ras-association domain family protein 1A (RASSF1A) in breast cancer cells.
  • To elucidate the molecular mechanisms underlying curcumin's action on RASSF1A methylation and expression.

Main Methods:

  • Treatment of MCF-7 breast cancer cells with curcumin.
  • Analysis of RASSF1A mRNA and protein levels.
  • Assessment of RASSF1A promoter methylation.
  • Measurement of DNA methyltransferase 1 (DNMT1) expression and DNA methylation activity.
  • Investigation of the NF-κB/Sp1 complex interaction with the DNMT1 promoter.

Main Results:

  • Curcumin enhanced RASSF1A mRNA and protein levels in breast cancer cells.
  • Curcumin decreased RASSF1A promoter methylation.
  • Curcumin reduced DNA methylation activity and DNMT1 expression in MCF-7 cells.
  • Curcumin disrupted the NF-κB/Sp1 complex binding to the DNMT1 promoter.

Conclusions:

  • Curcumin reactivates the hypermethylation-silenced RASSF1A TSG in breast cancer cells.
  • Curcumin exerts its chemopreventive effects through hypomethylation-induced RASSF1A reactivation.
  • Curcumin's mechanism involves downregulating DNMT1 via disruption of the NF-κB/Sp1 complex.

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