Effect of sodium dichloroacetate on apoptotic gene expression in human leukemia cell lines

Pharmacol Rep. 2019 Apr;71(2):248-256. doi: 10.1016/j.pharep.2018.12.003. Epub 2018 Dec 12.

Abstract

Background: Sodium dichloroacetate (DCA) is an agent with anticancer properties against solid tumors. DCA also seems to have antileukemic activity. In order to affirm it we investigate the effect of DCA on cell viability and apoptotic gene expression profiles in leukemia cell lines: CEM/C1, CCRF/CEM, HL-60, HL-60/MX2.

Methods: Cell viability was assessed by trypan blue staining. The expression of 93 genes involved in the process of apoptosis was determined by real-time PCR method using Taqman Low Density Array (TLDA).

Results: CEM/C1, CCRF/CEM, HL-60, HL-60/MX2 cells were exposed to DCA for 24 h. The sensitivity of each cell line to DCA is different and depends on the concentration. CEM/C1 was the most sensitive with an half-maximal inhibitory concentration (IC50) value of 30 mM, while HL-60/MX2 was the most resistant with an IC50 value of 75 mM. Exposure of leukemia cells to DCA causes differences in gene expression profiles which cannot indicate that any particular pathway of apoptosis is initiated. However, the presence of 388 statistically significant correlations between expression pattern of gens was determined.

Conclusion: We showed that DCA causes a decrease in viability of leukemia cells. The decline depends on DCA concentration. The induction of any particular apoptosis pathway is not shown in cells after DCA treatment. For that reason, studies on the molecular mechanism of cell death after exposure to DCA should be continued.

Keywords: Apoptosis; Cell cultures; DCA; Leukemia.

MeSH terms

  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects*
  • Cell Line, Tumor
  • Cell Survival / drug effects*
  • Dichloroacetic Acid / administration & dosage
  • Dichloroacetic Acid / pharmacology*
  • Gene Expression Regulation, Neoplastic / drug effects
  • HL-60 Cells
  • Humans
  • Inhibitory Concentration 50
  • Leukemia / drug therapy*
  • Leukemia / pathology
  • Real-Time Polymerase Chain Reaction

Substances

  • Antineoplastic Agents
  • Dichloroacetic Acid