Daidzein induces MCF-7 breast cancer cell apoptosis via the mitochondrial pathway

Ann Oncol. 2010 Feb;21(2):263-268. doi: 10.1093/annonc/mdp499. Epub 2009 Nov 4.

Abstract

Background: In order to study the anticancer effects and cellular apoptosis pathways induced by daidzein.

Materials and methods: We used the human MCF-7 breast cancer cell line as a model and examined the apoptosis by Hoechst-propidium iodide staining fluorescence imaging and flow cytometry.

Results: Our data indicated that daidzein induces antiproliferative effects in a concentration- and time-dependent manner. We demonstrated that daidzein-induced apoptosis in MCF-7 cells was initiated by the generation of reactive oxygen species (ROS). Furthermore, we showed that this daidzein-induced ROS generation was accompanied by disruption of mitochondrial transmembrane potential, down-regulation of bcl-2, and up-regulation of bax, which led to the release of cytochrome C from the mitochondria into the cytosol, which, in turn, resulted in the activation of caspase-9 and caspase-7, and ultimately in cell death. The induction of the mitochondrial caspase-dependent pathway was confirmed by pretreatment with pan-caspase inhibitor z-VAD-fmk and antioxidant N-acetyl-L-cysteine.

Conclusion: Accordingly, daidzein could induce breast cancer cell apoptosis through the mitochondrial caspase-dependent cell death pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology
  • Apoptosis / drug effects*
  • Breast Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical
  • Female
  • Humans
  • Isoflavones / pharmacology*
  • Membrane Potential, Mitochondrial / drug effects
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Mitochondria / physiology
  • Phytoestrogens / pharmacology
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Time Factors
  • Up-Regulation / drug effects

Substances

  • Antineoplastic Agents, Phytogenic
  • Isoflavones
  • Phytoestrogens
  • Reactive Oxygen Species
  • daidzein