1-Methylxanthine enhances the radiosensitivity of tumor cells

Autor:	Yeon Hee Kook, Hyewon Youn, Eun Kyung Choi, Eun-Taex Oh, Chulhee Kim, Byung Uk Lim, Heon Joo Park, Seong-Yun Jeong
Rok vydání:	2009
Předmět:	G2 Phase Radiation-Sensitizing Agents Cyclin-dependent kinase 1 Radiological and Ultrasound Technology DNA damage Kinase Apoptosis Cell cycle Biology Molecular biology Histones Cell Line Tumor Neoplasms Xanthines Cancer cell Humans cdc25 Phosphatases Radiology Nuclear Medicine and imaging Radiosensitivity Tumor Suppressor Protein p53 Clonogenic assay DNA Damage
Zdroj:	International Journal of Radiation Biology. 85:167-174
ISSN:	1362-3095 0955-3002
DOI:	10.1080/09553000902741190
Popis:	To determine the efficacy of a caffeine derivative 1-methylxanthine (1-MTX) in increasing radiosensitivity of cancer cells and elucidate the underlying mechanisms in vitro.RKO human colorectal cancer cells carrying wild type protein 53 kDa (p53) were incubated with 3 mM 1-MTX for 30 min, exposed to 4 Gy ionizing radiation, and further incubated with 1-MTX for three days. The clonogenic cell death was determined, and the cell cycle distribution and apoptosis were studied with flow cytometry at different times after irradiation. The DNA double strand break (DNA DSB) was examined using phosphorylated Histone2A (gamma-H2AX) foci formation, and the expression/activity of checkpoint 2 kinase (Chk2), cell division cycle 25 (Cdc25) phosphatase and cyclin B1/Cdc2 kinase were also investigated using western blotting and in vitro kinase assays.The treatment with 3 mM 1-MTX increased the radiation-induced clonogenic and apoptotic cell death. The radiation-induced phosphorylation of Chk2 and Cdc25c and the radiation-induced increase in the cyclin B1/Cdc2 kinas activity were little affected by 1-MTX. The radiation-induced G2/M arrest was only slightly shortened and the expression of radiation-induced gamma-H2AX was markedly prolonged by 1-MTX.1-MTX significantly increased the radiosensitivity of RKO human colorectal cancer cells carrying wild type p53 mainly by inhibiting the repair of radiation-induced DNA DSB without causing significant alteration in radiation-induced G2/M arrest. Such a radiosensitization occurred at 1-MTX concentrations almost non-toxic to the target tumor cells.
Databáze:	OpenAIRE
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