A well-tolerated anticonvulsant agent, valproic acid (VA), has been recently shown to inhibit histone deacetylases (HDACs), which in turn are involved in regulating the expression of estrogen receptor (ER) alpha by suppressing gene transcription. As estrogens are known to increase cell proliferation of human endometrial tumors, in this study we investigated whether treatments with VA increase the proliferative response of human endometrial adenocarcinoma cells to 17-betaestradiol (E2) through the induction of ER-alpha. The results clearly show that VA, at concentrations of clinical interest, markedly enhanced the proliferative activity exerted by E2 in the endometrial adenocarcinoma Ishikawa cell line. Moreover, in these cells treatments with VA resulted in increased ER-alpha gene expression. Similar effects of VA on cell proliferation were also observed in ER-alpha positive breast cancer cell lines (MCF-7). These findings indicate that VA might favor proliferation of estrogen-dependent human tumors.
Graziani, G., Tentori, L., Portarena, I., Vergati, M., Preziosi, P., Navarra, P. (2003). Valproic acid increases the stimulatory effects of estrogens on proliferation of human endometrial adenocarcinoma cells. ??????? it.cilea.surplus.oa.citation.tipologie.CitationProceedings.prensentedAt ??????? AUTUMN MEETING OF THE BELGIAN SOCIETY OF FUNDAMENTAL AND CLINICAL PHYSIOLOGY AND PHARMOCOLOGY, Gent, Belgio.
Valproic acid increases the stimulatory effects of estrogens on proliferation of human endometrial adenocarcinoma cells
GRAZIANI, GRAZIA;TENTORI, LUCIO;
2003-01-01
Abstract
A well-tolerated anticonvulsant agent, valproic acid (VA), has been recently shown to inhibit histone deacetylases (HDACs), which in turn are involved in regulating the expression of estrogen receptor (ER) alpha by suppressing gene transcription. As estrogens are known to increase cell proliferation of human endometrial tumors, in this study we investigated whether treatments with VA increase the proliferative response of human endometrial adenocarcinoma cells to 17-betaestradiol (E2) through the induction of ER-alpha. The results clearly show that VA, at concentrations of clinical interest, markedly enhanced the proliferative activity exerted by E2 in the endometrial adenocarcinoma Ishikawa cell line. Moreover, in these cells treatments with VA resulted in increased ER-alpha gene expression. Similar effects of VA on cell proliferation were also observed in ER-alpha positive breast cancer cell lines (MCF-7). These findings indicate that VA might favor proliferation of estrogen-dependent human tumors.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
