Dehydroepiandrosterone antiestrogenic action through androgen receptor in MCF-7 human breast cancer cell line.
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.
Boccuzzi
G
G
Department of Clinical Pathophisiology, University of Turin, Italy.
Di Monaco
M
M
Brignardello
E
E
Leonardi
L
L
Gatto
V
V
Pizzini
A
A
Gallo
M
M
D001943:Breast Neoplasms; D002455:Cell Division / Q000187:drug effects*; D003687:Dehydroepiandrosterone / Q000633:toxicity*; D004054:Diethylstilbestrol / Q000494:pharmacology; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000633:toxicity*; D005260:Female; D005485:Flutamide / Q000031:analogs & derivatives* / Q000494:pharmacology*; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D011944:Receptors, Androgen / Q000187:drug effects / Q000378:metabolism*; D013629:Tamoxifen / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D004965:Estrogen Antagonists; D011944:Receptors, Androgen; D013629:Tamoxifen; C014290:hydroxyflutamide; D003687:Dehydroepiandrosterone; D004958:Estradiol; D004054:Diethylstilbestrol; D005485:Flutamide; D005954:Glucosephosphate Dehydrogenase