Dehydroepiandrosterone antiestrogenic action through androgen receptor in MCF-7 human breast cancer cell line

Anticancer Res. Nov-Dec 1993;13(6A):2267-72.

Abstract

The possible mechanisms of the inhibitory effect of Dehydroepiandrosterone (DHEA) on the estrogen-induced growth of MCF-7 human breast cancer cells were explored. The impairment of metabolic pathways, via the inhibition of glucose-6-phosphate dehydrogenase (G6PD) activity, was excluded: G6PD activity in MCF-7 homogenate was reduced by DHEA only at a very high concentration (50 microM), while no inhibitory action on the enzyme activity was detected when DHEA was added at the antimitotic concentrations (0.02-0.5 microM). A steroid receptor mediated effect was explored: DHEA might either activate androgen receptors (AR) or partially displace E2 from estrogen receptor (ER). The pure antiandrogens Flutamide and Hydroxyflutamide reversed the inhibitory effect of DHEA on MCF-7 cell growth, whereas both the nonsteroidal estrogen Diethylstilbestrol and the antiestrogen Tamoxifen were ineffective. Results demonstrate that the AR activation plays a pivotal role in the inhibitory action of DHEA on the E2-induced MCF-7 growth.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms
  • Cell Division / drug effects*
  • Dehydroepiandrosterone / toxicity*
  • Diethylstilbestrol / pharmacology
  • Estradiol / metabolism
  • Estradiol / pharmacology
  • Estrogen Antagonists / toxicity*
  • Female
  • Flutamide / analogs & derivatives*
  • Flutamide / pharmacology*
  • Glucosephosphate Dehydrogenase / metabolism
  • Humans
  • Kinetics
  • Receptors, Androgen / drug effects
  • Receptors, Androgen / metabolism*
  • Tamoxifen / pharmacology
  • Tumor Cells, Cultured

Substances

  • Estrogen Antagonists
  • Receptors, Androgen
  • Tamoxifen
  • hydroxyflutamide
  • Dehydroepiandrosterone
  • Estradiol
  • Diethylstilbestrol
  • Flutamide
  • Glucosephosphate Dehydrogenase