Romidepsin induces caspase-dependent cell death in human neuroblastoma cells
| dc.contributor.author | Hegarty, Shane V. | |
| dc.contributor.author | Togher, Katie L. | |
| dc.contributor.author | O'Leary, Eimear | |
| dc.contributor.author | Solger, Franziska | |
| dc.contributor.author | Sullivan, Aideen M. | |
| dc.contributor.author | O'Keeffe, Gerard W. | |
| dc.contributor.funder | Irish Research Council | en |
| dc.contributor.funder | National University of Ireland | en |
| dc.contributor.funder | Science Foundation Ireland | en |
| dc.date.accessioned | 2017-09-01T10:25:29Z | |
| dc.date.available | 2017-09-01T10:25:29Z | |
| dc.date.issued | 2017-05-12 | |
| dc.date.updated | 2017-09-01T09:24:16Z | |
| dc.description.abstract | Neuroblastoma is the most common extracranial pediatric solid tumor, arising from the embryonic sympathoadrenal lineage of the neural crest, and is responsible for 15% of childhood cancer deaths. Although survival rates are good for some patients, those children diagnosed with high-risk neuroblastoma have survival rates as low as 35%. Thus, neuroblastoma remains a significant clinical challenge and the development of novel therapeutic strategies is essential. Given that there is widespread epigenetic dysregulation in neuroblastoma, epigenetic pharmacotherapy holds promise as a therapeutic approach. In recent years, histone deacetylase (HDAC) inhibitors, which cause selective activation of gene expression, have been shown to be potent chemotherapeutics for the treatment of a wide range of cancers. Here we examined the ability of the FDA-approved drug Romidepsin, a selective HDAC1/2 inhibitor, to act as a cytotoxic agent in neuroblastoma cells. Treatment with Romidepsin at concentrations in the low nanomolar range induced neuroblastoma cell death through caspase-dependent apoptosis. Romidepsin significantly increased histone acetylation, and significantly enhanced the cytotoxic effects of the cytotoxic agent 6-hydroxydopamine, which has been shown to induce cell death in neuroblastoma cells through increasing reactive oxygen species. Romidepsin was also more potent in MYCN-amplified neuroblastoma cells, which is an important prognostic marker of poor survival. This study has thus demonstrated that the FDA-approved chemotherapeutic drug Romidepsin has a potent caspase-dependent cytotoxic effect on neuroblastoma cells, whose effects enhance cell death induced by other cytotoxins, and suggests that Romidepsin may be a promising chemotherapeutic candidate for the treatment of neuroblastoma. | en |
| dc.description.sponsorship | Irish Research Council (R15897); National University of Ireland (R16189); Science Foundation Ireland (Grant Number 15/CDA/3498) | en |
| dc.description.status | Peer reviewed | en |
| dc.description.version | Accepted Version | en |
| dc.format.mimetype | application/pdf | en |
| dc.identifier.citation | Hegarty, S. V., Togher, K. L., O'Leary, E., Solger, F., Sullivan, A. M. and O'Keeffe, G. W. (2017) 'Romidepsin induces caspase-dependent cell death in human neuroblastoma cells', Neuroscience Letters, 653, pp. 12-18. doi:10.1016/j.neulet.2017.05.025 | en |
| dc.identifier.doi | 10.1016/j.neulet.2017.05.025 | |
| dc.identifier.endpage | 18 | en |
| dc.identifier.issn | 0304-3940 | |
| dc.identifier.journaltitle | Neuroscience Letters | en |
| dc.identifier.startpage | 12 | en |
| dc.identifier.uri | https://hdl.handle.net/10468/4602 | |
| dc.identifier.volume | 653 | en |
| dc.language.iso | en | en |
| dc.publisher | Elsevier Ltd | en |
| dc.rights | © 2017, Elsevier Ltd. All rights reserved. This manuscript version is made available under the CC-BY-NC-ND 4.0 license. | en |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | en |
| dc.subject | Romidepsin | en |
| dc.subject | Neuroblastoma | en |
| dc.subject | Cell death | en |
| dc.subject | Epigenetic regulation | en |
| dc.subject | Chemotherapeutic drug | en |
| dc.title | Romidepsin induces caspase-dependent cell death in human neuroblastoma cells | en |
| dc.type | Article (peer-reviewed) | en |
