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Imatinib mesylate elicits extracellular signal-related kinase (ERK) activation and enhances the survival of γ-irradiated epithelial cells

Lee, Jeeyong, Ko, Jiwon, Kim, Hyun-Ji, Im, Hyuntaik, Kim, Eun Ju, Yi, Jae Youn
Biochemical and biophysical research communications 2018 v.506 no.4 pp. 939-943
antineoplastic agents, apoptosis, cell lines, cell viability, epithelial cells, epithelium, gamma radiation, keratinocytes, mitogen-activated protein kinase, neoplasm cells, neoplasms, protective effect, radiation resistance, skin (animal), tyrosine
Imatinib mesylate, commercially known as Gleevec/Glivec, is the first targeted anticancer drug that inhibits activity of the tyrosine kinases, c-ABL, c-KIT, and PDGFR. A number of studies have shown that treatment with imatinib mesylate elicits extracellular signal-related kinase (ERK) activation, which, in turn, has been shown to confer radioresistance. Here, we investigated whether treatment with imatinib mesylate protects skin-derived epithelial cells, including normal keratinocytes, immortalized HaCaT and A431 cancer cell lines, from the effects of γ-radiation. ERK activation was detected 30 min after imatinib mesylate treatment in all three cell lines. In cells exposed to γ-irradiation in the presence of imatinib mesylate, this activation of ERK was associated with a reduction in radiation-induced apoptosis and enhanced cell survival. Similar effects of imatinib mesylate treatment were observed following γ-irradiation of a three-dimensional human skin culture system that reproduces a fully differentiated epithelium. Collectively, our findings provide the evidence of a protective effect of imatinib mesylate against the effects of γ-irradiation on epithelial-derived cells, regardless of their malignancy status.