Induction of Apoptosis in Human Leukemic Cell Lines by Diallyl Disulfide via Modulation of EGFR/ERK/PKM2 Signaling Pathways

Asian Pac J Cancer Prev. 2015;16(8):3509-15. doi: 10.7314/apjcp.2015.16.8.3509.

Abstract

Background: Diallyl disulfide (DADS) may exert potent anticancer action both in vitro and in vivo. Although its effects on cancer are significant, the underlying mechanisms remain unknown. In this study, we sought to elucidate possible links between DADS and pyruvate kinase (PKM2).

Materials and methods: KG1α, a leukemia cell line highly expressing PKM2 was used with a cell counting kit (CCK)-8 and flow cytometry (FCM) to investigate the effects of DADS. Relationships between PKM2 and DADS associated with phosphorylation of EGFR, ERK1/2 and MEK, were assessed by western blot analysis.

Results: In KG1α cells highly expressing PKM2, we found that DADS could affect proliferation, apoptosis and EGFR/ERK/PKM2 signaling pathways, abrogating EGF-induced nuclear accumulation of PKM2.

Conclusions: These results suggested that DADS suppressed the proliferation of KG1α cells, providing evidence that its proapoptotic effects are mediated through the inhibition of EGFR/ERK/PKM2 signaling pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allyl Compounds / pharmacology*
  • Anticarcinogenic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Blotting, Western
  • Carrier Proteins / drug effects*
  • Carrier Proteins / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Cell Survival / drug effects
  • Disulfides / pharmacology*
  • ErbB Receptors / drug effects*
  • ErbB Receptors / metabolism
  • HL-60 Cells
  • Humans
  • K562 Cells
  • Leukemia*
  • MAP Kinase Signaling System / drug effects*
  • Membrane Proteins / drug effects*
  • Membrane Proteins / metabolism
  • Mitogen-Activated Protein Kinase 1 / drug effects
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / drug effects
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Signal Transduction / drug effects
  • Thyroid Hormone-Binding Proteins
  • Thyroid Hormones / metabolism

Substances

  • Allyl Compounds
  • Anticarcinogenic Agents
  • Carrier Proteins
  • Disulfides
  • Membrane Proteins
  • Thyroid Hormones
  • diallyl disulfide
  • EGFR protein, human
  • ErbB Receptors
  • MAPK1 protein, human
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3