Synergistic growth inhibition in HL-60 cells by the combination of acyclic retinoid and vitamin K2

J Cancer Res Clin Oncol. 2011 May;137(5):779-87. doi: 10.1007/s00432-010-0938-0. Epub 2010 Jul 31.

Abstract

Purpose: The aim of this study was to assess the effects of acyclic retinoid (ACR) and vitamin K(2) (VK(2)) in HL-60 cells.

Methods: We used HL-60 cells, and the Trypan Blue dye exclusion method was used for cell proliferation assays. For detection of apoptosis, the Annexin V-binding capacity of treated cells was examined by flow cytometry. To evaluate the cell cycle, we used a FITC BrdU Flow KIT and flow cytometry. Total extracted and equivalent amounts of protein were examined by Western blotting using specific antibodies.

Results: ACR and VK(2) dose dependently inhibited the proliferation of HL-60 cells. These two agents in combination synergistically inhibited cell growth and induced apoptosis. VK(2) inhibited activation of the Ras/MAPK signaling pathway, and ACR plus VK(2) cooperatively inhibited phosphorylation of RXRα and the growth of HL-60 cells. Moreover, ACR and VK(2) induced increases in G0/G1 phase HL-60 cells, alone and synergistically in combination.

Conclusion: The synergistic effects of ACR and VK(2) on HL-60 cells may provide a novel strategy for treating leukemia.

MeSH terms

  • Apoptosis / drug effects
  • Blotting, Western
  • Cell Proliferation / drug effects*
  • Drug Synergism
  • Extracellular Signal-Regulated MAP Kinases / physiology
  • HL-60 Cells
  • Humans
  • Retinoid X Receptor alpha / physiology
  • Retinoids / administration & dosage
  • Retinoids / pharmacology*
  • Vitamin K 2 / administration & dosage
  • Vitamin K 2 / pharmacology*

Substances

  • Retinoid X Receptor alpha
  • Retinoids
  • Vitamin K 2
  • (2E,4E,6E,10E)-3,7,11,15-tetramethyl-2,4,6,10,14-hexadecapentaenoic acid
  • Extracellular Signal-Regulated MAP Kinases