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


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.


CONCLUSIONS
AG490 inhibits the growth of some cancer cells and activates ERK in LS174T and HT-29 cells. ERK activation is unrelated to growth inhibition.
Saito
Koichi
K
Molecular Biology Laboratory, Akita Prefectural University, Akita 010-0195, Japan.
Iwashita
Jun
J
Murata
Jun
J
Abe
Tatsuya
T
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000201:enzymology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D048708:Cell Growth Processes / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D019073:HT29 Cells; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D020032:Tyrphostins / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D020032:Tyrphostins; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases