TY - JOUR AB - 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. AD - Department of Biochemistry and Genetics, University of Navarra School of Sciences, 31008 Pamplona, Spain Department of Neurosurgery, Hospital Complex of Navarra, 31008 Pamplona, Spain Department of Pathology, Hospital Complex of Navarra, 31008 Pamplona, Spain Molecular Pathology Research Unit, Department of Pathology, Virgen de la Salud Hospital, 45005 Toledo, Spain IdiPaz Research Unit, La Paz University Hospital, 28046 Madrid, Spain Department of Pathology, University of Navarra Clinic, 31008 Pamplona, Spain AU - De La Rosa,Javier AU - Urdiciain,Alejandro AU - Zazpe,Idoya AU - Zelaya,María ,V. AU - Meléndez,Bárbara AU - Rey,Juan ,A. AU - Idoate,Miguel ,A. AU - Castresana,Javier ,S. AU - De La Rosa,Javier AU - Urdiciain,Alejandro AU - Zazpe,Idoya AU - Zelaya,María ,V. AU - Meléndez,Bárbara AU - Rey,Juan ,A. AU - Idoate,Miguel ,A. AU - Castresana,Javier ,S. DA - 2020/01/01 DO - 10.3892/ijo.2019.4905 EP - 300 IS - 1 JO - Int J Oncol KW - 3‑deazaneplanocin A epigenetics enhancer of zeste homolog 2 glioblastoma histone deacetylase panobinostat PY - 2020 SN - 1019-6439 1791-2423 SP - 283 ST - The synergistic effect of DZ‑NEP, panobinostat and temozolomide reduces clonogenicity and induces apoptosis in glioblastoma cells T2 - International Journal of Oncology TI - The synergistic effect of DZ‑NEP, panobinostat and temozolomide reduces clonogenicity and induces apoptosis in glioblastoma cells UR - https://doi.org/10.3892/ijo.2019.4905 VL - 56 ER -