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Biochem Biophys Res Commun. 2018 Dec 2;506(4):939-943. doi: 10.1016/j.bbrc.2018.10.095. Epub 2018 Nov 3.

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

Author information

1
Division of Radiation Biomedical Research, Korea Institute of Radiological and Medical Sciences, Seoul, 01812, Republic of Korea.
2
Division of Radiation Biomedical Research, Korea Institute of Radiological and Medical Sciences, Seoul, 01812, Republic of Korea. Electronic address: yjy_71@kcch.re.kr.

Abstract

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.

KEYWORDS:

ERK; Epithelial cells; Imatinib mesylate; c-ABL; γ-irradiation

PMID:
30396570
DOI:
10.1016/j.bbrc.2018.10.095
[Indexed for MEDLINE]

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