Preclinical evaluation of the antineoplastic action of 5-aza-2'-deoxycytidine and different histone deacetylase inhibitors on human Ewing's sarcoma cells
<p>Abstract</p> <p>Background</p> <p>Most patients with advanced Ewing's sarcoma (EWS) respond poorly to conventional chemotherapy, indicating the need for new treatment approaches. Epigenetic events, such as promoter hypermethylation and chromatin histone deacetyl...
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| Format: | Article |
| Language: | English |
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BMC
2008-11-01
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| Series: | Cancer Cell International |
| Online Access: | http://www.cancerci.com/content/8/1/16 |
| _version_ | 1819137543132676096 |
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| author | Bernstein Mark L Momparler Richard L Hurtubise Annie |
| author_facet | Bernstein Mark L Momparler Richard L Hurtubise Annie |
| author_sort | Bernstein Mark L |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Most patients with advanced Ewing's sarcoma (EWS) respond poorly to conventional chemotherapy, indicating the need for new treatment approaches. Epigenetic events, such as promoter hypermethylation and chromatin histone deacetylation, silence the expression of tumor suppressor genes (TSGs) and play an important role in tumorigenesis. These epigenetic changes can be reversed by using 5-aza-2'-deoxycytidine (5AZA-CdR), a potent inhibitor of DNA methylation, in combination with an inhibitor of histone deacetylase (HDAC).</p> <p>Results</p> <p>Here, we used a clonogenic assay to evaluate the <it>in vitro </it>antineoplastic activity of 5AZA-CdR in combination with different HDAC inhibitors on EWS cells. We observed that the HDAC inhibitors, MS-275, trichostatin-A, phenylbutyrate, LAQ824 and depsipeptide, enhanced the antineoplastic action of 5AZA-CdR on EWS cells. The combination of 5AZA-CdR and MS-275 showed marked synergy, and was correlated with significant reactivation of the expression of two TSGs, E-cadherin and tumor suppressor lung cancer-1 (TSLC1), in a EWS cell line.</p> <p>Conclusion</p> <p>These results suggest the value of future clinical studies investigating the combination of 5AZA-CdR and MS-275 in patients with advanced EWS.</p> |
| first_indexed | 2024-12-22T10:52:32Z |
| format | Article |
| id | doaj.art-dc2560b99f744875bd013082c976eb29 |
| institution | Directory Open Access Journal |
| issn | 1475-2867 |
| language | English |
| last_indexed | 2024-12-22T10:52:32Z |
| publishDate | 2008-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj.art-dc2560b99f744875bd013082c976eb292022-12-21T18:28:44ZengBMCCancer Cell International1475-28672008-11-01811610.1186/1475-2867-8-16Preclinical evaluation of the antineoplastic action of 5-aza-2'-deoxycytidine and different histone deacetylase inhibitors on human Ewing's sarcoma cellsBernstein Mark LMomparler Richard LHurtubise Annie<p>Abstract</p> <p>Background</p> <p>Most patients with advanced Ewing's sarcoma (EWS) respond poorly to conventional chemotherapy, indicating the need for new treatment approaches. Epigenetic events, such as promoter hypermethylation and chromatin histone deacetylation, silence the expression of tumor suppressor genes (TSGs) and play an important role in tumorigenesis. These epigenetic changes can be reversed by using 5-aza-2'-deoxycytidine (5AZA-CdR), a potent inhibitor of DNA methylation, in combination with an inhibitor of histone deacetylase (HDAC).</p> <p>Results</p> <p>Here, we used a clonogenic assay to evaluate the <it>in vitro </it>antineoplastic activity of 5AZA-CdR in combination with different HDAC inhibitors on EWS cells. We observed that the HDAC inhibitors, MS-275, trichostatin-A, phenylbutyrate, LAQ824 and depsipeptide, enhanced the antineoplastic action of 5AZA-CdR on EWS cells. The combination of 5AZA-CdR and MS-275 showed marked synergy, and was correlated with significant reactivation of the expression of two TSGs, E-cadherin and tumor suppressor lung cancer-1 (TSLC1), in a EWS cell line.</p> <p>Conclusion</p> <p>These results suggest the value of future clinical studies investigating the combination of 5AZA-CdR and MS-275 in patients with advanced EWS.</p>http://www.cancerci.com/content/8/1/16 |
| spellingShingle | Bernstein Mark L Momparler Richard L Hurtubise Annie Preclinical evaluation of the antineoplastic action of 5-aza-2'-deoxycytidine and different histone deacetylase inhibitors on human Ewing's sarcoma cells Cancer Cell International |
| title | Preclinical evaluation of the antineoplastic action of 5-aza-2'-deoxycytidine and different histone deacetylase inhibitors on human Ewing's sarcoma cells |
| title_full | Preclinical evaluation of the antineoplastic action of 5-aza-2'-deoxycytidine and different histone deacetylase inhibitors on human Ewing's sarcoma cells |
| title_fullStr | Preclinical evaluation of the antineoplastic action of 5-aza-2'-deoxycytidine and different histone deacetylase inhibitors on human Ewing's sarcoma cells |
| title_full_unstemmed | Preclinical evaluation of the antineoplastic action of 5-aza-2'-deoxycytidine and different histone deacetylase inhibitors on human Ewing's sarcoma cells |
| title_short | Preclinical evaluation of the antineoplastic action of 5-aza-2'-deoxycytidine and different histone deacetylase inhibitors on human Ewing's sarcoma cells |
| title_sort | preclinical evaluation of the antineoplastic action of 5 aza 2 deoxycytidine and different histone deacetylase inhibitors on human ewing s sarcoma cells |
| url | http://www.cancerci.com/content/8/1/16 |
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