Valproic Acid Increases the Stimulatory Effect of Estrogens on Proliferation of Human Endometrial Adenocarcinoma Cells

Long-term use of valproic acid (VA), a well-tolerated anticonvulsant agent widely used for treating epilepsia, has been recently shown to inhibit histone deacetylases, which in turn are involved in the regulation of the expression of estrogen receptor α (ERα) by suppressing gene transcription. Becau...

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Bibliographic Details
Published in:Endocrinology (Philadelphia) 2003-07, Vol.144 (7), p.2822-2828
Main Authors: Graziani, Grazia, Tentori, Lucio, Portarena, Ilaria, Vergati, Matteo, Navarra, Pierluigi
Format: Article
Language:English
Subjects:
17β-Estradiol
Adenocarcinoma
Anticonvulsants
Biological and medical sciences
Cell Division - drug effects
Cell proliferation
Drug Synergism
Endometrial Neoplasms
Endometrium
Enzyme Inhibitors - pharmacology
Estradiol - pharmacology
Estrogen Receptor alpha
Estrogen Receptor beta
Estrogen receptors
Estrogens
Female
Fundamental and applied biological sciences. Psychology
Gene expression
Gene Expression - drug effects
Gene regulation
Histones
Humans
Receptors, Estrogen - genetics
Sex hormones
Tumor Cells, Cultured - cytology
Tumor Cells, Cultured - drug effects
Tumors
Valproic acid
Valproic Acid - pharmacology
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Summary:Long-term use of valproic acid (VA), a well-tolerated anticonvulsant agent widely used for treating epilepsia, has been recently shown to inhibit histone deacetylases, which in turn are involved in the regulation of the expression of estrogen receptor α (ERα) by suppressing gene transcription. Because estrogens are known to increase cell proliferation of human endometrial tumors, in this study we investigated whether treatment with VA may increase the proliferative response of human endometrial adenocarcinoma cells to 17-β-estradiol through induction of ERα. The results clearly show that VA, at concentrations of clinical interest, significantly enhanced the proliferative activity exerted by 17-β-estradiol in the endometrial adenocarcinoma Ishikawa cell line. Moreover, in these cells treatment with VA resulted in increased ERα gene expression. Similar effects of VA on cell proliferation were also observed in an ERα-positive breast cancer cell line (MCF-7). These findings indicate that VA might favor proliferation of estrogen-dependent human tumors.
ISSN:0013-7227
1945-7170
DOI:10.1210/en.2002-0180