Document Detail


Estrogen metabolite 2-methoxyestradiol induces apoptosis and inhibits cell proliferation and collagen production in rat and human leiomyoma cells: a potential medicinal treatment for uterine fibroids.
MedLine Citation:
PMID:  17088081     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: The current study sought to investigate the effect of the estrogen metabolite 2-methoxyestradiol (2-MeOHE(2)) on apoptosis, cell proliferation, and collagen synthesis in human and rat leiomyoma cells. METHODS: [(3)H] thymidine and [(3)H] proline incorporation studies were conducted. The expression of vascular endothelial growth factor (VEGF), cyclin D1, Bcl-2, and Bax were evaluated by Western blot. Flow cytometry analysis was used to study the effect of 2-MeOHE(2) on apoptosis and the cell cycle. RESULTS: Compared with untreated controls, treatment of rat leiomyoma (ELT3) cells with 2-MeOHE(2) (0.1, 1, 2, 5, or 10 muM) reduced cell proliferation by 17%, 52%, 61%, 73%, and 79%, respectively (P <.05). Similarly, in human uterine leiomyoma cell line (huLM) cells, proliferation was reduced by 4%, 18%, 37%, 41%, and 51%, respectively. 2-MeOHE(2) also caused a concentration-dependent inhibition of collagen synthesis by 4%, 16%, 23%, 51%, and 70%, respectively, in huLM cells (P <.05). Cell cycle analysis indicated that 2-MeOHE(2) treatment (1 to 5 muM) in huLM cells resulted in G(2)/M cell cycle arrest and a 45% increase in apoptosis compared with untreated control (P <.05). Western immunoblotting analysis indicated that 2-MeOHE(2) induces a concentration-dependent reduction in the expression of cyclin D1, Bcl-2, and VEGF proteins in both rat and human leiomyoma cell lines. CONCLUSIONS: This study provides the first evidence that 2-MeOHE(2) is a potent antiproliferative/apoptotic and collagen synthesis inhibiting agent in human and rat leiomyoma cells. To the best of our knowledge, this is the first report showing the potential use of 2-methoxyestradiol as a nonsurgical alternative therapy for uterine leiomyomas.
Authors:
Salama A Salama; Abdelhakim Ben Nasr; Raghvendra K Dubey; Ayman Al-Hendy
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2006-11-07
Journal Detail:
Title:  Journal of the Society for Gynecologic Investigation     Volume:  13     ISSN:  1556-7117     ISO Abbreviation:  J. Soc. Gynecol. Investig.     Publication Date:  2006 Dec 
Date Detail:
Created Date:  2006-12-20     Completed Date:  2007-01-16     Revised Date:  2007-12-03    
Medline Journal Info:
Nlm Unique ID:  9433806     Medline TA:  J Soc Gynecol Investig     Country:  United States    
Other Details:
Languages:  eng     Pagination:  542-50     Citation Subset:  IM    
Affiliation:
Department of Obstetrics & Gynecology, University of Texas Medical Branch, Galveston, Texas.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antimitotic Agents / pharmacology*
Apoptosis / drug effects*
Cell Line, Tumor
Cell Proliferation / drug effects*
Collagen / biosynthesis,  drug effects*
Estradiol / analogs & derivatives*,  pharmacology
Estrogens / metabolism
Female
Humans
Leiomyoma / drug therapy*
Rats
Uterine Neoplasms / drug therapy*
Grant Support
ID/Acronym/Agency:
R01 HD046228/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
0/Antimitotic Agents; 0/Estrogens; 362-07-2/2-methoxyestradiol; 50-28-2/Estradiol; 9007-34-5/Collagen

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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