The synergistic effect of DZ‑NEP, panobinostat and temozolomide reduces clonogenicity and induces apoptosis in glioblastoma cells
Current treatment against glioblastoma consists of surgical resection followed by temozolomide, with or without combined radiotherapy. Glioblastoma frequently acquires resistance to chemotherapy and/or radiotherapy. Novel therapeutic approaches are thus required. The inhibition of enhancer of zeste...
| Autores: | , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2020 |
| País: | España |
| Institución: | Universidad de Navarra |
| Repositorio: | Dadun. Depósito Académico Digital de la Universidad de Navarra |
| Idioma: | inglés |
| OAI Identifier: | oai:dadun.unav.edu:10171/68389 |
| Acceso en línea: | https://hdl.handle.net/10171/68389 |
| Access Level: | acceso abierto |
| Palabra clave: | 3-deazaneplanocin A Epigenetics Enhancer of zeste homolog 2 Glioblastoma Histone deacetylase Panobinostat |
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The synergistic effect of DZ‑NEP, panobinostat and temozolomide reduces clonogenicity and induces apoptosis in glioblastoma cellsDe-La-Rosa, J. (Javier)|||/items/d420f6f9-e470-4a26-8fb9-4c419c32a40aUrdiciain-Ezpeleta, A. (Alejandro)|||/items/7173bee2-0d3d-4431-a892-d92d60c667b0Zazpe, I. (Idoya)|||/items/0b5eae6f-50f8-41ed-a4c6-d0c071a44858Zelaya, M.V. (María Victoria)|||/items/b17ebd92-1f01-4512-b71f-4f05874ca7b3Meléndez, B. (Bárbara)|||/items/9c1f8587-8f9d-4f08-b10e-91b3670a0ffcRey, J.A. (Juan A.)|||/items/b33f46ba-e920-49a9-af7e-1d6566759c16Idoate, M.A. (Miguel Ángel)|||/items/7b905180-f34f-450d-934f-8bf7652f84d3Saez-Castresana, J. (Javier)|||/items/52f31ab0-8555-470d-af21-e677a1b3eff83-deazaneplanocin AEpigeneticsEnhancer of zeste homolog 2GlioblastomaHistone deacetylasePanobinostatCurrent treatment against glioblastoma consists of surgical resection followed by temozolomide, with or without combined radiotherapy. Glioblastoma frequently acquires resistance to chemotherapy and/or radiotherapy. Novel therapeutic approaches are thus required. The inhibition of enhancer of zeste homolog 2 (EZH2; a histone methylase) and histone deacetylases (HDACs) are possible epigenetic treatments. Temozolomide, 3-deazaneplanocin A (DZ-Nep; an EZH2 inhibitor) and panobinostat (an HDAC inhibitor) were tested in regular and temozolomide-resistant glioblastoma cells to confirm whether the compounds could behave in a synergistic, additive or antagonistic manner. A total of six commercial cell lines, two temozolomide-induced resistant cell lines and two primary cultures derived from glioblastoma samples were used. Cell lines were exposed to single treatments of the drugs in addition to all possible two- and three-drug combinations. Colony formation assays, synergistic assays and reverse transcription-quantitative PCR analysis of apoptosis-associated genes were performed. The highest synergistic combination was DZ-Nep + panobinostat. Triple treatment was also synergistic. Reduced clonogenicity and increased apoptosis were both induced. It was concluded that the therapeutic potential of the combination of these three drugs in glioblastoma was evident and should be further explored.Spandidos publicationsDadun. Depósito Académico Digital Universidad de Navarra20242024-01-1720202020-01-0120202020-01-01journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10171/68389reponame:Dadun. Depósito Académico Digital de la Universidad de Navarrainstname:Universidad de NavarraInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:dadun.unav.edu:10171/683892026-06-21T12:47:57Z |
| dc.title.none.fl_str_mv |
The synergistic effect of DZ‑NEP, panobinostat and temozolomide reduces clonogenicity and induces apoptosis in glioblastoma cells |
| title |
The synergistic effect of DZ‑NEP, panobinostat and temozolomide reduces clonogenicity and induces apoptosis in glioblastoma cells |
| spellingShingle |
The synergistic effect of DZ‑NEP, panobinostat and temozolomide reduces clonogenicity and induces apoptosis in glioblastoma cells De-La-Rosa, J. (Javier)|||/items/d420f6f9-e470-4a26-8fb9-4c419c32a40a 3-deazaneplanocin A Epigenetics Enhancer of zeste homolog 2 Glioblastoma Histone deacetylase Panobinostat |
| title_short |
The synergistic effect of DZ‑NEP, panobinostat and temozolomide reduces clonogenicity and induces apoptosis in glioblastoma cells |
| title_full |
The synergistic effect of DZ‑NEP, panobinostat and temozolomide reduces clonogenicity and induces apoptosis in glioblastoma cells |
| title_fullStr |
The synergistic effect of DZ‑NEP, panobinostat and temozolomide reduces clonogenicity and induces apoptosis in glioblastoma cells |
| title_full_unstemmed |
The synergistic effect of DZ‑NEP, panobinostat and temozolomide reduces clonogenicity and induces apoptosis in glioblastoma cells |
| title_sort |
The synergistic effect of DZ‑NEP, panobinostat and temozolomide reduces clonogenicity and induces apoptosis in glioblastoma cells |
| dc.creator.none.fl_str_mv |
De-La-Rosa, J. (Javier)|||/items/d420f6f9-e470-4a26-8fb9-4c419c32a40a Urdiciain-Ezpeleta, A. (Alejandro)|||/items/7173bee2-0d3d-4431-a892-d92d60c667b0 Zazpe, I. (Idoya)|||/items/0b5eae6f-50f8-41ed-a4c6-d0c071a44858 Zelaya, M.V. (María Victoria)|||/items/b17ebd92-1f01-4512-b71f-4f05874ca7b3 Meléndez, B. (Bárbara)|||/items/9c1f8587-8f9d-4f08-b10e-91b3670a0ffc Rey, J.A. (Juan A.)|||/items/b33f46ba-e920-49a9-af7e-1d6566759c16 Idoate, M.A. (Miguel Ángel)|||/items/7b905180-f34f-450d-934f-8bf7652f84d3 Saez-Castresana, J. (Javier)|||/items/52f31ab0-8555-470d-af21-e677a1b3eff8 |
| author |
De-La-Rosa, J. (Javier)|||/items/d420f6f9-e470-4a26-8fb9-4c419c32a40a |
| author_facet |
De-La-Rosa, J. (Javier)|||/items/d420f6f9-e470-4a26-8fb9-4c419c32a40a Urdiciain-Ezpeleta, A. (Alejandro)|||/items/7173bee2-0d3d-4431-a892-d92d60c667b0 Zazpe, I. (Idoya)|||/items/0b5eae6f-50f8-41ed-a4c6-d0c071a44858 Zelaya, M.V. (María Victoria)|||/items/b17ebd92-1f01-4512-b71f-4f05874ca7b3 Meléndez, B. (Bárbara)|||/items/9c1f8587-8f9d-4f08-b10e-91b3670a0ffc Rey, J.A. (Juan A.)|||/items/b33f46ba-e920-49a9-af7e-1d6566759c16 Idoate, M.A. (Miguel Ángel)|||/items/7b905180-f34f-450d-934f-8bf7652f84d3 Saez-Castresana, J. (Javier)|||/items/52f31ab0-8555-470d-af21-e677a1b3eff8 |
| author_role |
author |
| author2 |
Urdiciain-Ezpeleta, A. (Alejandro)|||/items/7173bee2-0d3d-4431-a892-d92d60c667b0 Zazpe, I. (Idoya)|||/items/0b5eae6f-50f8-41ed-a4c6-d0c071a44858 Zelaya, M.V. (María Victoria)|||/items/b17ebd92-1f01-4512-b71f-4f05874ca7b3 Meléndez, B. (Bárbara)|||/items/9c1f8587-8f9d-4f08-b10e-91b3670a0ffc Rey, J.A. (Juan A.)|||/items/b33f46ba-e920-49a9-af7e-1d6566759c16 Idoate, M.A. (Miguel Ángel)|||/items/7b905180-f34f-450d-934f-8bf7652f84d3 Saez-Castresana, J. (Javier)|||/items/52f31ab0-8555-470d-af21-e677a1b3eff8 |
| author2_role |
author author author author author author author |
| dc.contributor.none.fl_str_mv |
Dadun. Depósito Académico Digital Universidad de Navarra |
| dc.subject.none.fl_str_mv |
3-deazaneplanocin A Epigenetics Enhancer of zeste homolog 2 Glioblastoma Histone deacetylase Panobinostat |
| topic |
3-deazaneplanocin A Epigenetics Enhancer of zeste homolog 2 Glioblastoma Histone deacetylase Panobinostat |
| description |
Current treatment against glioblastoma consists of surgical resection followed by temozolomide, with or without combined radiotherapy. Glioblastoma frequently acquires resistance to chemotherapy and/or radiotherapy. Novel therapeutic approaches are thus required. The inhibition of enhancer of zeste homolog 2 (EZH2; a histone methylase) and histone deacetylases (HDACs) are possible epigenetic treatments. Temozolomide, 3-deazaneplanocin A (DZ-Nep; an EZH2 inhibitor) and panobinostat (an HDAC inhibitor) were tested in regular and temozolomide-resistant glioblastoma cells to confirm whether the compounds could behave in a synergistic, additive or antagonistic manner. A total of six commercial cell lines, two temozolomide-induced resistant cell lines and two primary cultures derived from glioblastoma samples were used. Cell lines were exposed to single treatments of the drugs in addition to all possible two- and three-drug combinations. Colony formation assays, synergistic assays and reverse transcription-quantitative PCR analysis of apoptosis-associated genes were performed. The highest synergistic combination was DZ-Nep + panobinostat. Triple treatment was also synergistic. Reduced clonogenicity and increased apoptosis were both induced. It was concluded that the therapeutic potential of the combination of these three drugs in glioblastoma was evident and should be further explored. |
| publishDate |
2020 |
| dc.date.none.fl_str_mv |
2020 2020-01-01 2020 2020-01-01 2024 2024-01-17 |
| dc.type.none.fl_str_mv |
journal article http://purl.org/coar/resource_type/c_6501 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/10171/68389 |
| url |
https://hdl.handle.net/10171/68389 |
| dc.language.none.fl_str_mv |
Inglés eng |
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Inglés |
| language |
eng |
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open access http://purl.org/coar/access_right/c_abf2 |
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info:eu-repo/semantics/openAccess |
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open access http://purl.org/coar/access_right/c_abf2 |
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openAccess |
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application/pdf |
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Spandidos publications |
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Spandidos publications |
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reponame:Dadun. Depósito Académico Digital de la Universidad de Navarra instname:Universidad de Navarra |
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Universidad de Navarra |
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Dadun. Depósito Académico Digital de la Universidad de Navarra |
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Dadun. Depósito Académico Digital de la Universidad de Navarra |
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1869421891340468224 |
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15,300719 |