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  • Title: The tyrosine kinase inhibitor AG490 inhibits growth of cancer cells and activates ERK in LS174T and HT-29 cells.
    Author: Saito K, Iwashita J, Murata J, Abe T.
    Journal: Anticancer Res; 2006; 26(2A):1085-90. PubMed ID: 16619510.
    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.
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