Retinoid X receptor alpha is highly phosphorylated in retinoic acid-resistant HL-60R cells and the combination of 9-cis retinoic acid plus MEK inhibitor induces apoptosis in the cells

Leuk Res. 2008 Jun;32(6):884-92. doi: 10.1016/j.leukres.2007.11.005. Epub 2007 Dec 20.

Abstract

We examined the effects of 9-cis retinoic acid (RA) on the expression levels of retinoid X receptor alpha (RXR alpha) and its phosphorylated form (p-RXR alpha) in HL-60 and HL-60R cells. 9-cis RA reduced both RXR alpha and p-RXR alpha in HL-60 cells, but did neither in HL-60R cells. However, when the HL-60R cells were treated with the combination of 9-cis RA plus PD98059, MEK inhibitor, the p-RXR alpha and RXR alpha proteins all markedly decreased. Moreover, the combination of those agents induced apoptosis in HL-60R cells. Phosphorylation of RXR alpha might be associated with RA-resistance in HL-60R cells.

MeSH terms

  • Alitretinoin
  • Apoptosis / drug effects*
  • Apoptosis / physiology
  • Blotting, Western
  • Butadienes / pharmacology
  • Cell Proliferation / drug effects
  • Drug Resistance, Neoplasm*
  • Drug Therapy, Combination
  • Enzyme Inhibitors / pharmacology
  • Flavonoids / pharmacology
  • HL-60 Cells
  • Humans
  • Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors*
  • Mitogen-Activated Protein Kinase Kinases / metabolism
  • Nitriles / pharmacology
  • Phosphorylation / drug effects
  • Retinoid X Receptor alpha / metabolism*
  • Tretinoin / pharmacology*

Substances

  • Butadienes
  • Enzyme Inhibitors
  • Flavonoids
  • Nitriles
  • Retinoid X Receptor alpha
  • U 0126
  • Alitretinoin
  • Tretinoin
  • Mitogen-Activated Protein Kinase Kinases
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one