Berberine, an isoquinoline alkaloid, inhibits the metastatic potential of breast cancer cells via Akt pathway modulation

J Agric Food Chem. 2012 Sep 26;60(38):9649-58. doi: 10.1021/jf302832n. Epub 2012 Sep 14.

Abstract

Berberine (BBR) is a natural alkaloid with significant antitumor activities against many types of cancer cells. In this study, we investigated the molecular mechanisms by which BBR repressed the metastatic potential of breast cancer cells. BBR was found to downregulate the enzymatic activities and expression levels of matrix metalloproteinases 2 and 9 (MMP2 and MMP9, respectively). The BBR-mediated suppression of MMP2 and MMP9 involved the inhibition of the Akt/nuclear factor kappa B (NF-κB) and activator protein-1 (AP-1) signaling pathways. Furthermore, BBR repressed the expression of the Akt protein by modulating the mRNA expression level and protein degradation of Akt. In conclusion, this study suggests that BBR can reduce the metastatic potential of highly metastatic breast cancer cells and may be a useful adjuvant therapeutic agent in the treatment of breast cancer by targeting the Akt pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology
  • Berberine / pharmacology*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Cell Adhesion / drug effects
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Survival / drug effects
  • Drug Screening Assays, Antitumor
  • Female
  • Humans
  • MCF-7 Cells / drug effects
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Matrix Metalloproteinase Inhibitors / pharmacology
  • NF-kappa B / metabolism
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction / drug effects
  • Transcription Factor AP-1 / metabolism

Substances

  • Antineoplastic Agents, Phytogenic
  • Matrix Metalloproteinase Inhibitors
  • NF-kappa B
  • Transcription Factor AP-1
  • Berberine
  • Proto-Oncogene Proteins c-akt
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9