Synergisitic and Antagonistic AML Cell Type-specific Responses to 5-Aza-2-deoxycitidine and 1-h-D-Arabinofuranoside

Anticancer Res. 2016 Feb;36(2):691-6.

Abstract

Background: The search for synergistic drug combinations is critical to the treatment of drug-resistant cancer, such as acute myeloid leukemia (AML). Characterizing RNA expression associated with 5-aza-2'-deoxycytidine (DAC) and 1-h-D-arabinofuranosylcytosine (Ara-C) is a critical step to increase the efficacy of their combinatorial therapies.

Materials and methods: After 72 h of single-dose treatments of AML cells with DAC or Ara-C, the half-maximal effective concentration of DAC and Ara-C and the drug combination index were assessed.

Results: Pre-treatment with DAC restores cellular sensitivity in Ara-C-resistant AML cells. In contrast, DAC/Ara-C combinations are antagonistic in other Ara-C-sensitive AML cells.

Conclusion: Our results provide an alternative approach for predicting what combinations, dosing and scheduling of drug delivery should be used to better individualize therapy of AML.

Keywords: Drug interaction; myeloid leukemia; pediatric cancer.

MeSH terms

  • Antimetabolites, Antineoplastic / pharmacology*
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Azacitidine / analogs & derivatives*
  • Azacitidine / pharmacology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cytarabine / pharmacology*
  • Decitabine
  • Dose-Response Relationship, Drug
  • Drug Resistance, Neoplasm
  • Drug Synergism
  • Humans
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / pathology
  • Time Factors

Substances

  • Antimetabolites, Antineoplastic
  • Cytarabine
  • Decitabine
  • Azacitidine