A selective serotonin 5-HT1B receptor inhibition suppresses cells proliferation and induces apoptosis in human uterine leiomyoma cells

Nilgun Gurbuz, Mehmet Resit Asoglu, Ahmed A. Ashour, Salama Salama, Gokhan Kilic, Bulent Ozpolat

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Objective Uterine leiomyomas (fibroids or myomas) are the most common pelvic tumor in women with about 70% lifetime incidence rate. Currently, the only definitive treatment is surgery, causing undesirable side effects and negative impact on women's quality of life, reproductive ability, and a substantial impact on healthcare costs. Therefore, curative medical treatments are needed to be developed. In this study, we investigated the impact of serotonin receptor 5-HT1B on cell proliferation and survival in human uterine leiomyoma cells (huLM). Study design The impact of 5-HT1B receptor on cell proliferation, survival and apoptosis was investigated using a selective 5-HTR1B antagonist SB216641 in huLM cells, utilizing MTS, colony formation assay and Annexin V staining, respectively. Mechanisms of inhibition of cell proliferation, survival and induction of apoptosis were investigated by Western blot analysis after treatment with various doses of HT1B antagonist. Results 5-HT1B receptor inhibition leads to a significant decrease in proliferation and colony formation in huLM cells, reduction of cyclin D1 and alpha-smooth muscle actin (α-SMA) expressions and the activity of Mitogen Activated Protein Kinase (MAPK) ERK and Elongation Factor 2 kinase (EF2K) pathways. 5-HT1B receptor blockage also induces apoptotic cell death by inducing cleavage of caspase-8, -9, and -3 and PARP. Conclusion Our findings show for the first time that 5-HT1B receptor promotes uterine leiomyoma cell survival and proliferation and its inhibition may be a potential therapeutic approach for human uterine leiomyomas. Thus, 5-HT1B expression and antagonists should be further investigated in leiomyoma tumors.

Original languageEnglish (US)
Pages (from-to)114-119
Number of pages6
JournalEuropean Journal of Obstetrics Gynecology and Reproductive Biology
Volume206
DOIs
StatePublished - Nov 1 2016

Fingerprint

Receptor, Serotonin, 5-HT1B
Leiomyoma
Cell Proliferation
Apoptosis
Cell Survival
Elongation Factor 2 Kinase
Serotonin 5-HT1 Receptor Antagonists
Myoma
Caspase 9
Caspase 8
Annexin A5
Cyclin D1
Therapeutics
Mitogen-Activated Protein Kinases
Health Care Costs
Smooth Muscle
Actins
Neoplasms
Cell Death
Western Blotting

Keywords

  • 5-HT
  • 5-Hydroxytriptamine
  • Antagonist
  • Apoptosis
  • Cyclin D1
  • EF2K
  • ERK
  • Fibroid
  • MAPK
  • Myoma
  • Proliferation
  • Receptor
  • SB216641
  • Serotonin
  • Survival
  • Treatment
  • Uterine leiomyoma

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynecology

Cite this

A selective serotonin 5-HT1B receptor inhibition suppresses cells proliferation and induces apoptosis in human uterine leiomyoma cells. / Gurbuz, Nilgun; Asoglu, Mehmet Resit; Ashour, Ahmed A.; Salama, Salama; Kilic, Gokhan; Ozpolat, Bulent.

In: European Journal of Obstetrics Gynecology and Reproductive Biology, Vol. 206, 01.11.2016, p. 114-119.

Research output: Contribution to journalArticle

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abstract = "Objective Uterine leiomyomas (fibroids or myomas) are the most common pelvic tumor in women with about 70{\%} lifetime incidence rate. Currently, the only definitive treatment is surgery, causing undesirable side effects and negative impact on women's quality of life, reproductive ability, and a substantial impact on healthcare costs. Therefore, curative medical treatments are needed to be developed. In this study, we investigated the impact of serotonin receptor 5-HT1B on cell proliferation and survival in human uterine leiomyoma cells (huLM). Study design The impact of 5-HT1B receptor on cell proliferation, survival and apoptosis was investigated using a selective 5-HTR1B antagonist SB216641 in huLM cells, utilizing MTS, colony formation assay and Annexin V staining, respectively. Mechanisms of inhibition of cell proliferation, survival and induction of apoptosis were investigated by Western blot analysis after treatment with various doses of HT1B antagonist. Results 5-HT1B receptor inhibition leads to a significant decrease in proliferation and colony formation in huLM cells, reduction of cyclin D1 and alpha-smooth muscle actin (α-SMA) expressions and the activity of Mitogen Activated Protein Kinase (MAPK) ERK and Elongation Factor 2 kinase (EF2K) pathways. 5-HT1B receptor blockage also induces apoptotic cell death by inducing cleavage of caspase-8, -9, and -3 and PARP. Conclusion Our findings show for the first time that 5-HT1B receptor promotes uterine leiomyoma cell survival and proliferation and its inhibition may be a potential therapeutic approach for human uterine leiomyomas. Thus, 5-HT1B expression and antagonists should be further investigated in leiomyoma tumors.",
keywords = "5-HT, 5-Hydroxytriptamine, Antagonist, Apoptosis, Cyclin D1, EF2K, ERK, Fibroid, MAPK, Myoma, Proliferation, Receptor, SB216641, Serotonin, Survival, Treatment, Uterine leiomyoma",
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T1 - A selective serotonin 5-HT1B receptor inhibition suppresses cells proliferation and induces apoptosis in human uterine leiomyoma cells

AU - Gurbuz, Nilgun

AU - Asoglu, Mehmet Resit

AU - Ashour, Ahmed A.

AU - Salama, Salama

AU - Kilic, Gokhan

AU - Ozpolat, Bulent

PY - 2016/11/1

Y1 - 2016/11/1

N2 - Objective Uterine leiomyomas (fibroids or myomas) are the most common pelvic tumor in women with about 70% lifetime incidence rate. Currently, the only definitive treatment is surgery, causing undesirable side effects and negative impact on women's quality of life, reproductive ability, and a substantial impact on healthcare costs. Therefore, curative medical treatments are needed to be developed. In this study, we investigated the impact of serotonin receptor 5-HT1B on cell proliferation and survival in human uterine leiomyoma cells (huLM). Study design The impact of 5-HT1B receptor on cell proliferation, survival and apoptosis was investigated using a selective 5-HTR1B antagonist SB216641 in huLM cells, utilizing MTS, colony formation assay and Annexin V staining, respectively. Mechanisms of inhibition of cell proliferation, survival and induction of apoptosis were investigated by Western blot analysis after treatment with various doses of HT1B antagonist. Results 5-HT1B receptor inhibition leads to a significant decrease in proliferation and colony formation in huLM cells, reduction of cyclin D1 and alpha-smooth muscle actin (α-SMA) expressions and the activity of Mitogen Activated Protein Kinase (MAPK) ERK and Elongation Factor 2 kinase (EF2K) pathways. 5-HT1B receptor blockage also induces apoptotic cell death by inducing cleavage of caspase-8, -9, and -3 and PARP. Conclusion Our findings show for the first time that 5-HT1B receptor promotes uterine leiomyoma cell survival and proliferation and its inhibition may be a potential therapeutic approach for human uterine leiomyomas. Thus, 5-HT1B expression and antagonists should be further investigated in leiomyoma tumors.

AB - Objective Uterine leiomyomas (fibroids or myomas) are the most common pelvic tumor in women with about 70% lifetime incidence rate. Currently, the only definitive treatment is surgery, causing undesirable side effects and negative impact on women's quality of life, reproductive ability, and a substantial impact on healthcare costs. Therefore, curative medical treatments are needed to be developed. In this study, we investigated the impact of serotonin receptor 5-HT1B on cell proliferation and survival in human uterine leiomyoma cells (huLM). Study design The impact of 5-HT1B receptor on cell proliferation, survival and apoptosis was investigated using a selective 5-HTR1B antagonist SB216641 in huLM cells, utilizing MTS, colony formation assay and Annexin V staining, respectively. Mechanisms of inhibition of cell proliferation, survival and induction of apoptosis were investigated by Western blot analysis after treatment with various doses of HT1B antagonist. Results 5-HT1B receptor inhibition leads to a significant decrease in proliferation and colony formation in huLM cells, reduction of cyclin D1 and alpha-smooth muscle actin (α-SMA) expressions and the activity of Mitogen Activated Protein Kinase (MAPK) ERK and Elongation Factor 2 kinase (EF2K) pathways. 5-HT1B receptor blockage also induces apoptotic cell death by inducing cleavage of caspase-8, -9, and -3 and PARP. Conclusion Our findings show for the first time that 5-HT1B receptor promotes uterine leiomyoma cell survival and proliferation and its inhibition may be a potential therapeutic approach for human uterine leiomyomas. Thus, 5-HT1B expression and antagonists should be further investigated in leiomyoma tumors.

KW - 5-HT

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KW - Antagonist

KW - Apoptosis

KW - Cyclin D1

KW - EF2K

KW - ERK

KW - Fibroid

KW - MAPK

KW - Myoma

KW - Proliferation

KW - Receptor

KW - SB216641

KW - Serotonin

KW - Survival

KW - Treatment

KW - Uterine leiomyoma

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JO - European Journal of Obstetrics and Gynecology and Reproductive Biology

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