title: Cooperation of the HDAC inhibitor vorinostat and radiation in metastatic neuroblastoma: efficacy and underlying mechanisms.
abstract: Histone deacetylase (HDAC) inhibitors can radiosensitize cancer cells. Radiation is critical in high-risk neuroblastoma treatment, and combinations of HDAC inhibitor vorinostat and radiation are proposed for neuroblastoma trials. Therefore, we investigated radiosensitizing effects of vorinostat in neuroblastoma. Treatment of neuroblastoma cell lines decreased cell viability and resulted in additive effects with radiation. In a murine metastatic neuroblastoma in vivo model vorinostat and radiation combinations decreased tumor volumes compared to single modality. DNA repair enzyme Ku-86 was reduced in several neuroblastoma cells treated with vorinostat. Thus, vorinostat potentiates anti-neoplastic effects of radiation in neuroblastoma possibly due to down-regulation of DNA repair enzyme Ku-86.
authors.affiliation: Department of Neurology, University of California, San Francisco, 505 Parnassus Avenue, San Francisco, CA 94143-0106, USA. muellers@neuropeds.ucsf.edu
authors.forename: Sabine
authors.initials: S
authors.lastname: Mueller
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Yang
authors.forename: Theo L
authors.initials: TL
authors.lastname: Sottero
authors.forename: Ashley
authors.initials: A
authors.lastname: Gragg
authors.forename: Gautam
authors.initials: G
authors.lastname: Prasad
authors.forename: Mei-Yin
authors.initials: MY
authors.lastname: Polley
authors.forename: William A
authors.initials: WA
authors.lastname: Weiss
authors.forename: Katherine K
authors.initials: KK
authors.lastname: Matthay
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Davidoff
authors.forename: Steven G
authors.initials: SG
authors.lastname: DuBois
authors.forename: Daphne A
authors.initials: DA
authors.lastname: Haas-Kogan
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D003131:Combined Modality Therapy; D045643:DNA Repair Enzymes / Q000378:metabolism; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000502:physiology; D005720:Gamma Rays; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use*; D006655:Histone Deacetylases / Q000737:chemistry / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000627:therapeutic use*; D008164:Luminescent Proteins / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009447:Neuroblastoma / Q000188:drug therapy* / Q000532:radiotherapy* / Q000556:secondary; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay; D000077337:Vorinostat
chemical_list: D051858:Forkhead Transcription Factors; C468783:H2AX protein, human; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; D008164:Luminescent Proteins; D011838:Radiation-Sensitizing Agents; C090140:Whn protein; D000077337:Vorinostat; D006655:Histone Deacetylases; D045643:DNA Repair Enzymes