Anti-cancer effects of curcumin on lung cancer through the inhibition of EZH2 and NOTCH1

Oncotarget. 2016 May 3;7(18):26535-50. doi: 10.18632/oncotarget.8532.

Abstract

Curcumin is potentially therapeutic for malignant diseases. The mechanisms of this effect might involve a combination of antioxidant, immunomodulatory, proapoptotic, and antiangiogenic activities. However, the exact mechanisms are not fully understood. In the present study, we provided evidences that curcumin suppressed the expression of enhancer of zeste homolog 2 (EZH2) in lung cancer cells both transcriptionally and post-transcriptionally. Curcumin inhibited the expression of EZH2 through microRNA (miR)-let 7c and miR-101. Curcumin decreased the expression of NOTCH1 through the inhibition of EZH2. There was a reciprocal regulation between EZH2 and NOTCH1 in lung cancer cells. These observations suggest that curcumin inhibits lung cancer growth and metastasis at least partly through the inhibition of EZH2 and NOTCH1.

Keywords: NOTCH1; curcumin; enhancer of zeste homolog 2; lung cancer; microRNA.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Curcumin / pharmacology*
  • Enhancer of Zeste Homolog 2 Protein / biosynthesis*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • Receptor, Notch1 / biosynthesis*

Substances

  • Antineoplastic Agents
  • NOTCH1 protein, human
  • Receptor, Notch1
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein
  • Curcumin