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

Salama A. Salama, Abdelhakim Ben Nasr, Raghvendra K. Dubey, Ayman Al-Hendy

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Abstract

Objective: The current study sought to investigate the effect of the estrogen metabolite 2-methoxyestradiol (2-MeOHE2) on apoptosis, cell proliferation, and collagen synthesis in human and rat leiomyoma cells. Methods: [3H] thymidine and [3H] 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-MeOHE2 on apoptosis and the cell cycle. Results: Compared with untreated controls, treatment of rat leiomyoma (ELT3) cells with 2-MeOHE2 (0.1, 1, 2, 5, or 10 μM) 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-MeOHE2 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-MeOHE2 treatment (1 to 5 μM) in huLM cells resulted in G2/M cell cycle arrest and a 45% increase in apoptosis compared with untreated control (P <.05). Western immunoblotting analysis indicated that 2-MeOHE2 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-MeOHE2 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.

Original languageEnglish (US)
Pages (from-to)542-550
Number of pages9
JournalJournal of the Society for Gynecologic Investigation
Volume13
Issue number8
DOIs
StatePublished - Dec 1 2006

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Leiomyoma
Estrogens
Collagen
Cell Proliferation
Apoptosis
Cyclin D1
Vascular Endothelial Growth Factor A
Cell Cycle
Western Blotting
G2 Phase Cell Cycle Checkpoints
Cell Line
Complementary Therapies
Proline
Thymidine
2-methoxyestradiol
Flow Cytometry
Therapeutics
Proteins

Keywords

  • 2-Methoxyestradiol
  • apoptosis
  • cell cycle
  • collagen synthesis
  • uterine leiomyoma

ASJC Scopus subject areas

  • Obstetrics and Gynecology

Cite this

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. / Salama, Salama A.; Nasr, Abdelhakim Ben; Dubey, Raghvendra K.; Al-Hendy, Ayman.

In: Journal of the Society for Gynecologic Investigation, Vol. 13, No. 8, 01.12.2006, p. 542-550.

Research output: Contribution to journalArticle

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title = "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",
abstract = "Objective: The current study sought to investigate the effect of the estrogen metabolite 2-methoxyestradiol (2-MeOHE2) on apoptosis, cell proliferation, and collagen synthesis in human and rat leiomyoma cells. Methods: [3H] thymidine and [3H] 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-MeOHE2 on apoptosis and the cell cycle. Results: Compared with untreated controls, treatment of rat leiomyoma (ELT3) cells with 2-MeOHE2 (0.1, 1, 2, 5, or 10 μM) 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-MeOHE2 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-MeOHE2 treatment (1 to 5 μM) in huLM cells resulted in G2/M cell cycle arrest and a 45{\%} increase in apoptosis compared with untreated control (P <.05). Western immunoblotting analysis indicated that 2-MeOHE2 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-MeOHE2 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.",
keywords = "2-Methoxyestradiol, apoptosis, cell cycle, collagen synthesis, uterine leiomyoma",
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T1 - Estrogen Metabolite 2-Methoxyestradiol Induces Apoptosis and Inhibits Cell Proliferation and Collagen Production in Rat and Human Leiomyoma Cells

T2 - A Potential Medicinal Treatment for Uterine Fibroids

AU - Salama, Salama A.

AU - Nasr, Abdelhakim Ben

AU - Dubey, Raghvendra K.

AU - Al-Hendy, Ayman

PY - 2006/12/1

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N2 - Objective: The current study sought to investigate the effect of the estrogen metabolite 2-methoxyestradiol (2-MeOHE2) on apoptosis, cell proliferation, and collagen synthesis in human and rat leiomyoma cells. Methods: [3H] thymidine and [3H] 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-MeOHE2 on apoptosis and the cell cycle. Results: Compared with untreated controls, treatment of rat leiomyoma (ELT3) cells with 2-MeOHE2 (0.1, 1, 2, 5, or 10 μM) 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-MeOHE2 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-MeOHE2 treatment (1 to 5 μM) in huLM cells resulted in G2/M cell cycle arrest and a 45% increase in apoptosis compared with untreated control (P <.05). Western immunoblotting analysis indicated that 2-MeOHE2 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-MeOHE2 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.

AB - Objective: The current study sought to investigate the effect of the estrogen metabolite 2-methoxyestradiol (2-MeOHE2) on apoptosis, cell proliferation, and collagen synthesis in human and rat leiomyoma cells. Methods: [3H] thymidine and [3H] 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-MeOHE2 on apoptosis and the cell cycle. Results: Compared with untreated controls, treatment of rat leiomyoma (ELT3) cells with 2-MeOHE2 (0.1, 1, 2, 5, or 10 μM) 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-MeOHE2 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-MeOHE2 treatment (1 to 5 μM) in huLM cells resulted in G2/M cell cycle arrest and a 45% increase in apoptosis compared with untreated control (P <.05). Western immunoblotting analysis indicated that 2-MeOHE2 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-MeOHE2 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.

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KW - cell cycle

KW - collagen synthesis

KW - uterine leiomyoma

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