A selective serotonin 5-HT 1B receptor inhibition suppresses cells proliferation and induces apoptosis in human uterine leiomyoma cells

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

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

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-HT 1B on cell proliferation and survival in human uterine leiomyoma cells (huLM). Study design The impact of 5-HT 1B receptor on cell proliferation, survival and apoptosis was investigated using a selective 5-HTR 1B 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 HT 1B antagonist. Results 5-HT 1B 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-HT 1B 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-HT 1B receptor promotes uterine leiomyoma cell survival and proliferation and its inhibition may be a potential therapeutic approach for human uterine leiomyomas. Thus, 5-HT 1B 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 and Gynecology and Reproductive Biology
Volume206
DOIs
StatePublished - Nov 1 2016

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

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