Differential Effects of In Vitro Treatment with Cinobufotalin on Three Types of Ovarian Cancer Cells

Anticancer Res. 2018 Oct;38(10):5717-5724. doi: 10.21873/anticanres.12909.

Abstract

Background/aim: Cinobufotalin (CINO), a cardiotonic steroid, has been used as an anticancer agent. This study assessed the cell-specific effect of CINO on SK-OV-3, CRL-1978 and CRL-11731 ovarian cancer cells which differ in terms of their respective karyotypes.

Materials and methods: Cell cultures were treated with CINO (0.1, 1, 5 and 10 μM) for 24, 48, and 72 h. Cell proliferation, migration, and invasion were measured using CellTiter, Cytoselect, and FluoroBlock assays, respectively. Expression of proliferating cell nuclear antigen (PCNA) was evaluated by western blot analysis. Cell viability was determined by fluorescence-activated cell sorting. Immunofluorescence was performed using Annexin-V staining and fluorescein isothiocyanate (FITC). Mitochondrial membrane potential (MMP) was measured using MitoTracker™ Red.

Results: CINO at 0.5 μM inhibited SK-OV-3, CRL-1978, and CRL-11731 proliferation, migration, and invasion. Each cell type differed in response to CINO doses for PCNA, Annexin-V expression and MMP.

Conclusion: The antineoplastic property of CINO is consistent, but its mode of action varies among cell lines.

Keywords: Ovarian cancer cell lines; apoptotic signaling; bufadienolide; cinobufotalin; migration; mitochondrial membrane potential; viability.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Bufanolides / pharmacology*
  • Cell Movement / drug effects*
  • Cell Proliferation / drug effects
  • Female
  • Humans
  • In Vitro Techniques
  • Membrane Potential, Mitochondrial / drug effects
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / pathology*
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Bufanolides
  • cinobufotalin