| Online-Ressource |
Verfasst von: | Vollmer, Johanna [VerfasserIn]  |
| Ecker, Jonas [VerfasserIn]  |
| Hielscher, Thomas [VerfasserIn]  |
| Valinciute, Gintvile [VerfasserIn]  |
| Ridinger, Johannes [VerfasserIn]  |
| Jamaladdin, Nora [VerfasserIn]  |
| Peterziel, Heike [VerfasserIn]  |
| Tilburg, Cornelis M. van [VerfasserIn]  |
| Oehme, Ina [VerfasserIn]  |
| Witt, Olaf [VerfasserIn]  |
| Milde, Till [VerfasserIn]  |
Titel: | Class I HDAC inhibition reduces DNA damage repair capacity of MYC-amplified medulloblastoma cells |
Verf.angabe: | Johanna Vollmer, Jonas Ecker, Thomas Hielscher, Gintvile Valinciute, Johannes Ridinger, Nora Jamaladdin, Heike Peterziel, Cornelis M. van Tilburg, Ina Oehme, Olaf Witt, Till Milde |
E-Jahr: | 2023 |
Jahr: | 3 October 2023 |
Umfang: | 16 S. |
Fussnoten: | Online veröffentlicht: 3. Oktober 2023 ; Gesehen am 04.01.2024 |
Titel Quelle: | Enthalten in: Journal of neuro-oncology |
Ort Quelle: | Dordrecht [u.a.] : Springer Science + Business Media B.V, 1983 |
Jahr Quelle: | 2023 |
Band/Heft Quelle: | 164(2023), 3, Seite 617-632 |
ISSN Quelle: | 1573-7373 |
Abstract: | Purpose: MYC-driven Group 3 medulloblastoma (MB) (subtype II) is a highly aggressive childhood brain tumor. Sensitivity of MYC-driven MB to class I histone deacetylase inhibitors (HDACi) has been previously demonstrated in vitro and in vivo. In this study we characterize the transcriptional effects of class I HDACi in MYC-driven MB and explore beneficial drug combinations. Methods: MYC-amplified Group 3 MB cells (HD-MB03) were treated with class I HDACi entinostat. Changes in the gene expression profile were quantified on a microarray. Bioinformatic assessment led to the identification of pathways affected by entinostat treatment. Five drugs interfering with these pathways (olaparib, idasanutlin, ribociclib, selinexor, vinblastine) were tested for synergy with entinostat in WST-8 metabolic activity assays in a 5 × 5 combination matrix design. Synergy was validated in cell count and flow cytometry experiments. The effect of entinostat and olaparib on DNA damage was evaluated by γH2A.X quantification in immunoblotting, fluorescence microscopy and flow cytometry. Results: Entinostat treatment changed the expression of genes involved in 22 pathways, including downregulation of DNA damage response. The PARP1 inhibitors olaparib and pamiparib showed synergy with entinostat selectively in MYC-amplified MB cells, leading to increased cell death, decreased viability and increased formation of double strand breaks, as well as increased sensitivity to additional induction of DNA damage by doxorubicin. Non-MYC-amplified MB cells and normal human fibroblasts were not susceptible to this triple treatment. Conclusion: Our study identifies the combination of entinostat with olaparib as a new potential therapeutic approach for MYC-driven Group 3 MB. |
DOI: | doi:10.1007/s11060-023-04445-w |
URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext: https://doi.org/10.1007/s11060-023-04445-w |
| DOI: https://doi.org/10.1007/s11060-023-04445-w |
Datenträger: | Online-Ressource |
Sprache: | eng |
Sach-SW: | DNA-damage |
| HDAC |
| Medulloblastoma |
| MYC |
| Synergy |
K10plus-PPN: | 1877274852 |
Verknüpfungen: | → Zeitschrift |
Class I HDAC inhibition reduces DNA damage repair capacity of MYC-amplified medulloblastoma cells / Vollmer, Johanna [VerfasserIn]; 3 October 2023 (Online-Ressource)