Δ(9)-Tetrahydrocannabinol disrupts estrogen-signaling through up-regulation of estrogen receptor ß (ERß).
Chem Res Toxicol
; 26(7): 1073-9, 2013 Jul 15.
Article
em En
| MEDLINE
| ID: mdl-23718638
ABSTRACT
Δ(9)-Tetrahydrocannabinol (Δ(9)-THC) has been reported as possessing antiestrogenic activity, although the mechanisms underlying these effects are poorly delineated. In this study, we used the estrogen receptor α (ERα)-positive human breast cancer cell line, MCF-7, as an experimental model and showed that Δ(9)-THC exposures markedly suppresses 17ß-estradiol (E2)- induced MCF-7 cell proliferation. We demonstrate that these effects result from Δ(9)-THC's ability to inhibit E2-liganded ERα activation. Mechanistically, the data obtained from biochemical analyses revealed that (i) Δ(9)-THC up-regulates ERß, a repressor of ERα, inhibiting the expression of E2/ERα-regulated genes that promote cell growth and that (ii) Δ(9)-THC induction of ERß modulates E2/ERα signaling in the absence of direct interaction with the E2 ligand binding site. Therefore, the data presented support the concept that Δ(9)-THC's antiestrogenic activities are mediated by the ERß disruption of E2/ERα signaling.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Dronabinol
/
Transdução de Sinais
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Regulação para Cima
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Receptor beta de Estrogênio
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Estrogênios
Limite:
Humans
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article