The tyrosine kinase inhibitor AG490 inhibits growth of cancer cells and activates ERK in LS174T and HT-29 cells

Anticancer Res. 2006 Mar-Apr;26(2A):1085-90.

Abstract

Background: The activity of tyrosine kinases, although strictly regulated in normal cells, is often disturbed in cancer cells. The inhibition of a tyrosine kinase could be a target for treating cancer.

Materials and methods: The colon cancer cell lines LS174T and HT-29 and the lung cancer cell line NCI-H292 were used. The cells were incubated with 100 microM of the tyrosine kinase inhibitor AG490 for 1-3 days and were examined for growth. Extracellular signal-regulated kinase (ERK) activation was detected by anti-phospho ERK antibodies. The cell cycle was analyzed by flow cytometry.

Results: AG490 inhibited the growth of LS174T, HT-29 and NCI-H292 cells without inducing apoptosis. Short-term treatment with AG490 activated ERK and p38 MAPK in the LS174T and HT-29 cells, but not in NCI-H292 cells. ERK activation, however, was unrelated to the growth inhibition in LS174T cells, because the inhibition persisted even after the prevention of ERK activation.

Conclusion: AG490 inhibits the growth of some cancer cells and activates ERK in LS174T and HT-29 cells. ERK activation is unrelated to growth inhibition.

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / enzymology
  • Antineoplastic Agents / pharmacology*
  • Cell Growth Processes / drug effects
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / enzymology
  • Colonic Neoplasms / pathology
  • Dose-Response Relationship, Drug
  • Enzyme Activation / drug effects
  • Enzyme Inhibitors / pharmacology*
  • Extracellular Signal-Regulated MAP Kinases / metabolism*
  • HT29 Cells
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / enzymology
  • Lung Neoplasms / pathology
  • Tyrphostins / pharmacology*
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Tyrphostins
  • alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide
  • Extracellular Signal-Regulated MAP Kinases
  • p38 Mitogen-Activated Protein Kinases