Ethyl Pyruvate Combats Human Leukemia Cells but Spares Normal Blood Cells

PLoS One. 2016 Aug 31;11(8):e0161571. doi: 10.1371/journal.pone.0161571. eCollection 2016.

Abstract

Ethyl pyruvate, a known ROS scavenger and anti-inflammatory drug was found to combat leukemia cells. Tumor cell killing was achieved by concerted action of necrosis/apoptosis induction, ATP depletion, and inhibition of glycolytic and para-glycolytic enzymes. Ethyl lactate was less harmful to leukemia cells but was found to arrest cell cycle in the G0/G1 phase. Both, ethyl pyruvate and ethyl lactate were identified as new inhibitors of GSK-3β. Despite the strong effect of ethyl pyruvate on leukemia cells, human cognate blood cells were only marginally affected. The data were compiled by immune blotting, flow cytometry, enzyme activity assay and gene array analysis. Our results inform new mechanisms of ethyl pyruvate-induced cell death, offering thereby a new treatment regime with a high therapeutic window for leukemic tumors.

MeSH terms

  • Adenosine Triphosphate / metabolism*
  • Adult
  • Female
  • Free Radical Scavengers / pharmacology*
  • G1 Phase Cell Cycle Checkpoints / drug effects*
  • Glycogen Synthase Kinase 3 beta / antagonists & inhibitors
  • Glycogen Synthase Kinase 3 beta / metabolism
  • Humans
  • K562 Cells
  • Leukemia / drug therapy*
  • Leukemia / metabolism
  • Leukemia / pathology
  • Male
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / metabolism
  • Pyruvates / pharmacology*

Substances

  • Free Radical Scavengers
  • Neoplasm Proteins
  • Pyruvates
  • ethyl pyruvate
  • Adenosine Triphosphate
  • GSK3B protein, human
  • Glycogen Synthase Kinase 3 beta

Grant support

The authors received no specific funding for this work.