DNMT (DNA methyltransferase) inhibitors radiosensitize human cancer cells by suppressing DNA repair activity
<p>Abstract</p> <p>Background</p> <p>Histone modifications and DNA methylation are two major factors in epigenetic phenomenon. Unlike the histone deacetylase inhibitors, which are known to exert radiosensitizing effects, there have only been a few studies thus far conce...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2012-03-01
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| Series: | Radiation Oncology |
| Subjects: | |
| Online Access: | http://www.ro-journal.com/content/7/1/39 |
| _version_ | 1818037786192642048 |
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| author | Kim Hak Jae Kim Jin Ho Chie Eui Kyu Da Young Park Kim In Ah Kim Il Han |
| author_facet | Kim Hak Jae Kim Jin Ho Chie Eui Kyu Da Young Park Kim In Ah Kim Il Han |
| author_sort | Kim Hak Jae |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Histone modifications and DNA methylation are two major factors in epigenetic phenomenon. Unlike the histone deacetylase inhibitors, which are known to exert radiosensitizing effects, there have only been a few studies thus far concerning the role of DNA methyltransferase (DNMT) inhibitors as radiosensitizers. The principal objective of this study was to evaluate the effects of DNMT inhibitors on the radiosensitivity of human cancer cell lines, and to elucidate the mechanisms relevant to that process.</p> <p>Methods</p> <p>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 γH2AX, a marker of radiation-induced DNA double-strand break, was examined by immunocytochemistry.</p> <p>Results</p> <p>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 γH2AX expression was observed in the cells treated with DNMT inhibitors prior to radiation as compared with those treated by radiation alone.</p> <p>Conclusions</p> <p>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.</p> |
| first_indexed | 2024-12-10T07:32:22Z |
| format | Article |
| id | doaj.art-f53bfbae50d4455787c356b2bbba59ab |
| institution | Directory Open Access Journal |
| issn | 1748-717X |
| language | English |
| last_indexed | 2024-12-10T07:32:22Z |
| publishDate | 2012-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Radiation Oncology |
| spelling | doaj.art-f53bfbae50d4455787c356b2bbba59ab2022-12-22T01:57:31ZengBMCRadiation Oncology1748-717X2012-03-01713910.1186/1748-717X-7-39DNMT (DNA methyltransferase) inhibitors radiosensitize human cancer cells by suppressing DNA repair activityKim Hak JaeKim Jin HoChie Eui KyuDa Young ParkKim In AhKim Il Han<p>Abstract</p> <p>Background</p> <p>Histone modifications and DNA methylation are two major factors in epigenetic phenomenon. Unlike the histone deacetylase inhibitors, which are known to exert radiosensitizing effects, there have only been a few studies thus far concerning the role of DNA methyltransferase (DNMT) inhibitors as radiosensitizers. The principal objective of this study was to evaluate the effects of DNMT inhibitors on the radiosensitivity of human cancer cell lines, and to elucidate the mechanisms relevant to that process.</p> <p>Methods</p> <p>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 γH2AX, a marker of radiation-induced DNA double-strand break, was examined by immunocytochemistry.</p> <p>Results</p> <p>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 γH2AX expression was observed in the cells treated with DNMT inhibitors prior to radiation as compared with those treated by radiation alone.</p> <p>Conclusions</p> <p>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.</p>http://www.ro-journal.com/content/7/1/39CancerEpigeneticsDNA methylationDNA methyltransferase inhibitorRadiosensitization |
| spellingShingle | Kim Hak Jae Kim Jin Ho Chie Eui Kyu Da Young Park Kim In Ah Kim Il Han DNMT (DNA methyltransferase) inhibitors radiosensitize human cancer cells by suppressing DNA repair activity Radiation Oncology Cancer Epigenetics DNA methylation DNA methyltransferase inhibitor Radiosensitization |
| title | DNMT (DNA methyltransferase) inhibitors radiosensitize human cancer cells by suppressing DNA repair activity |
| title_full | DNMT (DNA methyltransferase) inhibitors radiosensitize human cancer cells by suppressing DNA repair activity |
| title_fullStr | DNMT (DNA methyltransferase) inhibitors radiosensitize human cancer cells by suppressing DNA repair activity |
| title_full_unstemmed | DNMT (DNA methyltransferase) inhibitors radiosensitize human cancer cells by suppressing DNA repair activity |
| title_short | DNMT (DNA methyltransferase) inhibitors radiosensitize human cancer cells by suppressing DNA repair activity |
| title_sort | dnmt dna methyltransferase inhibitors radiosensitize human cancer cells by suppressing dna repair activity |
| topic | Cancer Epigenetics DNA methylation DNA methyltransferase inhibitor Radiosensitization |
| url | http://www.ro-journal.com/content/7/1/39 |
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