Additive Interaction of Cisplatin and Histone Deacetylase Inhibitors Combined Treatment in Rhabdomyosarcoma Cells - An Isobolographic Analysis

Anticancer Res. 2017 Mar;37(3):1067-1074. doi: 10.21873/anticanres.11418.

Abstract

Background/aim: The aim of this study was to assess the anticancer effect and the type of pharmacologic drug-drug interaction of cisplatin (CDDP) and histone deacetylase inhibitors (HDIs) combined treatment on the rhabdomyosarcoma cell line.

Materials and methods: The antiproliferative actions of cisplatin and suberoylanilide hydroxamic acid (SAHA, vorinostat), as well as valproic acid (VPA) alone and in combination, were evaluated using the tetrazolium dye-based MTT cell proliferation assay and isobolographic analysis.

Results: All tested compounds inhibited proliferation of rhabdomyosarcoma cancer cells in a dose-dependent manner. The combinations of CDDP with SAHA and CDDP with VPA produced additive interaction with type-I isobolographic analysis.

Conclusion: When adding SAHA or VPA to CDDP therapy, one can expect additive anticancer effects in the rhabdomyosarcoma cell line.

Keywords: Rhabdomyosarcoma; SAHA; VPA; cisplatin; histone deacetylase inhibitors; isobolographic analysis.

MeSH terms

  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Apoptosis / drug effects
  • Cell Line, Tumor / drug effects
  • Cell Proliferation
  • Cisplatin / administration & dosage*
  • Cisplatin / pharmacology
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Drug Screening Assays, Antitumor
  • Histone Deacetylase Inhibitors / administration & dosage*
  • Histone Deacetylase Inhibitors / pharmacology
  • Humans
  • Hydroxamic Acids / administration & dosage
  • Hydroxamic Acids / pharmacology
  • Inhibitory Concentration 50
  • Rhabdomyosarcoma / pathology*
  • Valproic Acid / administration & dosage
  • Valproic Acid / pharmacology
  • Vorinostat

Substances

  • Antineoplastic Agents
  • Histone Deacetylase Inhibitors
  • Hydroxamic Acids
  • Vorinostat
  • Valproic Acid
  • Cisplatin