Equol induces apoptosis through cytochrome c-mediated caspases cascade in human breast cancer MDA-MB-453 cells

Chem Biol Interact. 2009 Jan 15;177(1):7-11. doi: 10.1016/j.cbi.2008.09.031. Epub 2008 Oct 9.

Abstract

This study investigated the role of the caspase activation cascade in extrinsic and intrinsic apoptosis induced by equol in human breast cancer MDA-MB cells. First, the antiproliferative effect of equol was determined in cells treated with 1-100 microM equol for 24, 48, and 72h. Equol significantly inhibited cell proliferation in a dose-dependent manner (p<0.05). Exposure to 50 or 100 microM equol for 72h strongly promoted apoptosis. Under the same conditions, remarkable cytochrome c release was observed. Subsequently, caspase-9, which acts in mitochondria-mediated apoptosis, was cleaved by equol at high concentrations, but caspase-8 activation of receptor-mediated apoptosis was not observed. At both equol concentrations, the caspase-8 and -9 activity assays showed similar patterns. In addition, equol treatment activated caspase-3, which is downstream from caspase-9, and this was accompanied by the cleavage of capase-6 and -7. Activation of these caspases leads to increased activation of PARP, lamin, and ICAD. This study suggests that equol induces the intrinsic pathway of apoptosis via caspase-9 and cytochrome c, independent of caspase-8, in human breast cancer MDA-MB-453 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Breast Neoplasms / enzymology*
  • Breast Neoplasms / pathology*
  • Caspases / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cytochromes c / metabolism*
  • Enzyme Activation / drug effects
  • Equol
  • Humans
  • Isoflavones / pharmacology*

Substances

  • 4',7-dihydroxy-3,4-dihydroisoflavone
  • Isoflavones
  • Equol
  • Cytochromes c
  • Caspases