Genistein inhibits cell proliferation and stimulates apoptosis in human coronary artery endothelial cells

Gynecol Obstet Invest. 2013;75(4):235-42. doi: 10.1159/000345936. Epub 2013 Apr 11.

Abstract

Background/aims: Isoflavone genistein is a plant-derived compound structurally similar to estradiol, which behaves weakly estrogenic or anti-estrogenic in a cell- and concentration-dependent manner. Genistein has been hypothesized to have beneficial effects on vascular diseases, although the mechanism has been unclear. Here, we investigated whether genistein may play a role in atherogenesis by regulating human coronary artery endothelial cell (HCAEC) survival.

Methods: HCAECs obtained from 48- to 53-year-old women (n = 3) were used and immunocytochemistry, cell proliferation assay and apoptosis assay were carried on HCAECs treated by genistein.

Results: Immunocytochemistry confirmed that HCAECs in culture express predominantly ESR2. Cell proliferation assay revealed that following 72 h of genistein treatment, HCAEC proliferation decreased in a concentration-dependent (10(-10) to 10(-6)M) manner compared to control (p < 0.01). The anti-proliferative effect of genistein is inhibited by estradiol. Genistein (10(-8)M) also induced a time-dependent increase in the number of apoptotic HCAECs after 24-, 48- and 72-hour treatments as detected by TUNEL and morphological analyses.

Conclusion: These findings suggest that genistein acts as an anti-proliferative agent on HCAECs. The anti-proliferative and proapoptotic effects of genistein on vascular cells underlie the proposed anti-atherogenic and cardioprotective role of genistein.

MeSH terms

  • Apoptosis / drug effects
  • Cardiovascular Diseases / drug therapy
  • Cardiovascular Diseases / metabolism
  • Cardiovascular Diseases / pathology
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Coronary Vessels / cytology*
  • Dose-Response Relationship, Drug
  • Endothelial Cells / cytology*
  • Endothelial Cells / drug effects*
  • Endothelial Cells / metabolism
  • Estrogen Receptor alpha / metabolism
  • Estrogen Receptor beta / metabolism
  • Female
  • Genistein / pharmacology*
  • Humans
  • In Situ Nick-End Labeling
  • Middle Aged
  • Phytoestrogens / pharmacology*

Substances

  • ESR1 protein, human
  • Estrogen Receptor alpha
  • Estrogen Receptor beta
  • Phytoestrogens
  • Genistein