Thalidomide Inhibits Epidermal Growth Factor-Induced Cell Growth in Mouse and Human Monocytic Leukemia Cells via Ras Inactivation

Biochem Biophys Res Commun. 2008 Oct 3;374(4):683-7. doi: 10.1016/j.bbrc.2008.07.090. Epub 2008 Jul 26.

Abstract

The effect of thalidomide on epidermal growth factor (EGF)-induced cell growth was examined. Thalidomide inhibited EGF-induced cell growth in mouse and human monocytic leukemia cells, RAW 264.7, U937 and THP-1. Thalidomide inhibited EGF-induced phosphorylation of extracellular signal regulated kinase (ERK) 1/2, but not p38 and stress-activated protein kinase (SAPK)/JNK. The phosphorylation of MEK1/2 and Raf at Ser 338 as the upstream molecules of ERK 1/2 was also prevented by thalidomide. Further, it inhibited EGF-induced Ras activation through preventing the transition to GTP-bound active Ras. Thalidomide inhibited the Ras activation induced by lipopolysaccharide (LPS) and vascular endothelial growth factor (VEGF) as well as EGF. There was no significant difference in the expression and function of EGF receptor between thalidomide-treated and non-treated cells. Therefore, thalidomide was suggested to inhibit EGF-induced cell growth via inactivation of Ras.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / pharmacology*
  • Animals
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Enzyme Activation
  • Epidermal Growth Factor / antagonists & inhibitors*
  • Epidermal Growth Factor / pharmacology
  • ErbB Receptors / metabolism
  • Humans
  • Leukemia / enzymology*
  • Mice
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Monocytes / drug effects
  • Monocytes / enzymology
  • Phosphorylation
  • Thalidomide / pharmacology*
  • Vascular Endothelial Growth Factor A / pharmacology
  • p38 Mitogen-Activated Protein Kinases / metabolism
  • ras Proteins / antagonists & inhibitors*
  • ras Proteins / metabolism

Substances

  • Angiogenesis Inhibitors
  • Antineoplastic Agents
  • Vascular Endothelial Growth Factor A
  • Thalidomide
  • Epidermal Growth Factor
  • ErbB Receptors
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • p38 Mitogen-Activated Protein Kinases
  • ras Proteins