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Effects of salinomycin on human ovarian cancer cell line OV2008 are associated with modulating p38 MAPK

Bei Zhang1, Xueya Wang, Fengfeng Cai

  • 1Laboratory for Gynecologic Oncology, Women's Hospital/Department of Biomedicine, University of Basel, Hebelstrasse 20, 4031 Basel, Switzerland.

Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine
|July 10, 2012
PubMed

Insights

Salinomycin, a cancer stem cell inhibitor, effectively reduced ovarian cancer cell growth and induced apoptosis in vitro and in vivo. This anticancer effect may involve the activation of p38 mitogen-activated protein kinase (p38 MAPK).

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Ovarian cancer remains a leading cause of cancer-related deaths in women.
  • Cancer stem cells (CSCs) are implicated in tumor recurrence and therapeutic resistance.
  • Salinomycin is a known selective inhibitor of CSCs.

Purpose of the Study:

  • To investigate the anticancer effects of salinomycin on the human ovarian cancer cell line OV2008.
  • To elucidate the underlying mechanisms of salinomycin's action, including apoptosis induction and cell cycle modulation.
  • To evaluate salinomycin's efficacy in an in vivo ovarian cancer xenograft model.

Main Methods:

  • Cell viability was assessed using the resazurin reduction assay.
  • Apoptosis was visualized via 4,6-diamino-2-phenylindole staining and quantified by flow cytometry.
  • Cell cycle parameters were analyzed using flow cytometry.
  • p38 mitogen-activated protein kinase (p38 MAPK) phosphorylation was measured by Bio-Plex phosphoprotein assay.
  • In vivo efficacy was determined by monitoring tumor growth in ovarian xenografts.

Main Results:

  • Salinomycin demonstrated concentration- and time-dependent inhibition of OV2008 cell viability.
  • Salinomycin induced significant apoptosis in OV2008 cells, characterized by morphological changes.
  • No significant cell cycle arrest was observed in treated cells.
  • Salinomycin treatment led to enhanced phosphorylation of p38 MAPK.
  • Salinomycin significantly suppressed ovarian xenograft tumor growth in vivo.

Conclusions:

  • Salinomycin exhibits potent anticancer activity against human ovarian cancer cells (OV2008) both in vitro and in vivo.
  • The induction of apoptosis by salinomycin in OV2008 cells appears to be linked to the activation of the p38 MAPK signaling pathway.
  • These findings suggest salinomycin as a potential therapeutic agent for ovarian cancer, warranting further investigation.

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