Curcumin suppresses the TPA-induced invasion through inhibition of PKCα-dependent MMP-expression in MCF-7 human breast cancer cells

Phytomedicine. 2012 Sep 15;19(12):1085-92. doi: 10.1016/j.phymed.2012.07.002. Epub 2012 Aug 22.

Abstract

Curcumin (diferuloylmethane) is a polyphenol derived from the plant turmeric (Curcuma longa), which is commonly used as a spice. Although anti-carcinogenic, anti-oxidant, anti-inflammation, and anti-angiogenic properties have been reported, the effect of curcumin on breast cancer metastasis is unknown. Matrix metalloproteinase-9 (MMP-9) is a major component in cancer cell invasion. In this study, we investigated the inhibitory effect of curcumin on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced MMP-9 expression and cell invasion and the molecular mechanisms involved in MCF-7 cells. Our results showed that curcumin inhibits TPA-induced MMP-9 expression and cell invasion through suppressing NF-κB and AP-1 activation. Also, curcumin strongly repressed the TPA-induced phosphorylation of p38 and JNK and inhibited TPA-induced translocation of PKCα from the cytosol to the membrane, but did not affect the translocation of PKCδ. These results indicate that curcumin-mediated inhibition of TPA-induced MMP-9 expression and cell invasion involves the suppression of the PKCα, MAPK and NF-κB/AP-1 pathway in MCF-7 cells. Curcumin may have potential value in restricting breast cancer metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology
  • Antineoplastic Agents, Phytogenic / therapeutic use
  • Biological Transport / drug effects
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Movement / drug effects*
  • Curcuma / chemistry*
  • Curcumin / pharmacology
  • Curcumin / therapeutic use*
  • Female
  • Humans
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • MCF-7 Cells
  • Matrix Metalloproteinase 9 / metabolism*
  • NF-kappa B / metabolism
  • Neoplasm Metastasis / prevention & control
  • Phytotherapy*
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use
  • Protein Kinase C-alpha / metabolism*
  • Signal Transduction
  • Tetradecanoylphorbol Acetate
  • Transcription Factor AP-1 / metabolism
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Antineoplastic Agents, Phytogenic
  • NF-kappa B
  • Plant Extracts
  • Transcription Factor AP-1
  • Protein Kinase C-alpha
  • JNK Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • Matrix Metalloproteinase 9
  • Curcumin
  • Tetradecanoylphorbol Acetate