Effect of tamoxifen and retinoic acid on bradykinin induced proliferation in MCF-7 cells

J Cell Biochem. 2009 Feb 15;106(3):473-81. doi: 10.1002/jcb.22031.

Abstract

Chemopreventive approaches for the treatment of breast cancer have been validated clinically and with in vitro studies. The combined action of tamoxifen/all-trans retinoic acid was advantageous in MCF-7 cells, reducing cell proliferation, Bcl-2 and c-Myc protein levels and increasing E-Cadherin protein levels and Gap junctional Intercellular Communication. We further investigated their combined effect in the presence of bradykinin, a pro-inflammatory agent, previously reported to contribute to the proliferation of breast cancer cells. Bradykinin increased MCF-7 cell proliferation, c-Myc levels and ERK1/2 activity. The co-incubation of bradykinin-MCF-7 cells with tamoxifen/all-trans retinoic acid reduced cell proliferation, ERK1/2 activity, as well as Bcl-2, c-Myc, and bradykinin receptor-2 levels, without altering the enhanced E-cadherin levels induced by tamoxifen/all-trans retinoic acid. We showed that the anti-tumoral effect of tamoxifen/all-trans retinoic acid is beneficial in MCF-7 breast cancer cells grown in a bradykinin-pro-mitogenic environment, an effect that might be, at least in part, through the MAPK pathway and B2-bradykinin receptor inhibition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bradykinin / pharmacology*
  • Cadherins / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Humans
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Proto-Oncogene Proteins c-myc / metabolism
  • Receptor, Bradykinin B2 / metabolism
  • Signal Transduction / drug effects
  • Tamoxifen / pharmacology*
  • Tretinoin / pharmacology*

Substances

  • Cadherins
  • MYC protein, human
  • Proto-Oncogene Proteins c-bcl-2
  • Proto-Oncogene Proteins c-myc
  • Receptor, Bradykinin B2
  • Tamoxifen
  • Tretinoin
  • Bradykinin