DHEA for treatment of Breast Cancer


Cancer J. 2006 Mar-Apr;12(2):160-5.


DHEA-Induced Antiproliferative Effect in MCF-7 Cells Is Androgen- and
Estrogen Receptor-Independent.

Gayosso V, Montano LF, Lopez-Marure R.

Departmento de Biologia Celular, Instituto Nacional de Cardiologia "Ignacio
Chavez,", UNAM, Mexico City, Mexico.

Dehydroepiandrosterone, an adrenal hormone derived from cholesterol, can be
metabolized to estrogens (estradiol) and androgens (testosterone). In this
study, we evaluated whether the antiproliferative effect induced by
dehydroepiandrosterone in MCF-7 cells (an estrogen-dependent breast cancer
cell line) is direct, or indirect, through its conversion to estradiol or
testosterone. Although dehydroepiandrosterone had an antiproliferative
effect at supraphysiologic concentrations, when it was used at physiologic
concentrations, it increased the proliferation of MCF-7 cells.
17beta-estradiol induced an increase in MCF-7 cell proliferation at
physiologic concentrations, whereas testosterone had a weak inhibitory
effect at 100 muM. Dehydroepiandrosterone sulfate (its inactive sulfate
ester) had no effect upon the cell cycle. Dehydroepiandrosterone-induced
antiproliferative and proliferative effects were not blocked by inhibitors
of androgen or estrogen receptors, thus indicating that its effect is
secondary to a direct interaction with a "putative" receptor rather than a
conversion into steroid hormones. These results suggest that
dehydroepiandrosterone could be used at supraphysiologic concentrations in
the treatment of breast cancer.

.