7
尾-Hydroxy-epi
androst
erone (7
尾-OH-EpiA),
an endogenous
androgenic d
erivative of dehydroepi
androst
erone, has previously been shown to ex
ert
anti-inflammatory action
in vitro and
in vivo via a shift from prostagl
andin E2 (PGE2) to 15-deoxy-螖
12,14-PGJ2 production. This modulation in prostagl
andin production was obtained with low concentrations of 7
尾-OH-EpiA (1-100 nM)
and suggested that it might act through a specific receptor. Inflammation
and prostagl
andin synthesis is import
ant in the development
and survival of estrogen-dependent mammary c
anc
ers. Estrogen induced PGE2 production
and cell prolif
eration via its binding to estrogen receptors (ERs) in these tumors. Our objective was to test the effects of 7
尾-OH-EpiA on the prolif
eration (by counting with tryp
an blue exclusion), cell cycle
and cell apoptosis (by flow cytometry) of breast c
anc
er cell lines MCF-7 (ER伪+, ER
尾+, G-protein coupled receptor 30: GPR30+)
and MDA-MB-231 (ER伪鈭? ER
尾+, GPR30+)
and to identify a potential target of this st
eroid in these cell lineages (by tr
ansactivations)
and in the nuclear ER-negative SKBr3 cells (GPR30+) (by prolif
eration assays). 7
尾-OH-EpiA ex
erted
anti-estrogenic effects in MCF-7
and MDA-MB-231 cells associated with cell prolif
eration inhibition
and cell cycle arrest. Moreov
er, tr
ansactivation
and prolif
eration with ER
agonists assays indicated that 7
尾-OH-EpiA int
eracted with ER
尾. Data from prolif
eration assays on the MCF-7, MDA-MB-231
and SKBr3 cell lines suggested that 7
尾-OH-EpiA may also act through the membr
ane GPR30 receptor.
These results support that this androgenic steroid acts as an anti-estrogenic compound. Moreover, this is the first evidence that low doses of androgenic steroid exert antiproliferative effects in these mammary cancer cells. Further investigations are needed to improve understanding of the observed actions of endogenous 7尾-OH-EpiA.