%0 Journal Article
%T DNMT (DNA methyltransferase) inhibitors radiosensitize human cancer cells by suppressing DNA repair activity
%A Hak Jae Kim
%A Jin Ho Kim
%A Eui Kyu Chie
%A Park Da Young
%A In Ah Kim
%A Il Han Kim
%J Radiation Oncology
%D 2012
%I BioMed Central
%R 10.1186/1748-717x-7-39
%X A549 (lung cancer) and U373MG (glioblastoma) cells were exposed to radiation with or without six DNMT inhibitors (5-azacytidine, 5-aza-2'-deoxycytidine, zebularine, hydralazine, epigallocatechin gallate, and psammaplin A) for 18 hours prior to radiation, after which cell survival was evaluated via clonogenic assays. Cell cycle and apoptosis were analyzed via flow cytometry. Expressions of DNMT1, 3A/3B, and cleaved caspase-3 were detected via Western blotting. Expression of ¦ÃH2AX, a marker of radiation-induced DNA double-strand break, was examined by immunocytochemistry.Pretreatment with psammaplin A, 5-aza-2'-deoxycytidine, and zebularine radiosensitized both A549 and U373MG cells. Pretreatment with psammaplin A increased the sub-G1 fraction of A549 cells, as compared to cells exposed to radiation alone. Prolongation of ¦ÃH2AX expression was observed in the cells treated with DNMT inhibitors prior to radiation as compared with those treated by radiation alone.Psammaplin A, 5-aza-2'-deoxycytidine, and zebularine induce radiosensitivity in both A549 and U373MG cell lines, and suggest that this effect might be associated with the inhibition of DNA repair.Epigenetic alteration is one of the most important gene regulatory mechanisms. Unlike genetic alterations, epigenetic events are not changes in gene function that occur in conjunction with DNA sequence changes. Recently, epigenetic studies have been conducted in many different aspects of biology, and particularly in the cancer field. DNA methylation and histone modifications are two principal factors in epigenetic phenomena. These two mechanisms perform a crucial function in carcinogenesis and tumor progression.DNA methylation is controlled by DNA methyltransferase (DNMT), an enzyme that catalyzes the transfer of a methyl moiety from S-adenosyl-l-methionine to the 5-postion of cytosines in the CpG dinucleotide [1]. DNMT overexpression has been detected in a variety of malignancies, including lung, prostate, and colorect
%K Cancer
%K Epigenetics
%K DNA methylation
%K DNA methyltransferase inhibitor
%K Radiosensitization
%U http://www.ro-journal.com/content/7/1/39