title: A novel histone deacetylase inhibitor, CKD5, has potent anti-cancer effects in glioblastoma.
abstract: There have been extensive efforts to improve the outcome of glioblastoma, but the prognosis of this disease has not been significantly altered to date. Histone deacetylase inhibitors (HDACIs) have been evaluated as promising anti-cancer drugs and regulate cell growth, cell cycle arrest and apoptosis in glioblastoma. Here, we demonstrated the therapeutic efficacy of a novel pan-HDACI, 7-ureido-N-hydroxyheptanamide derivative (CKD5), compared with traditional pan-HDACIs, such as suberoylanilide hydroxamic acid (SAHA) and trichostatin A (TSA), in vitro and in vivo. Compared with SAHA and TSA, CKD5 had improved cytotoxic effects and induced apoptosis, anti-proliferative activity and cell cycle arrest at G2/M phase. Furthermore, CKD5 significantly reduced tumor volume and prolonged the survival in vivo compared with TSA, suggesting improved anti-cancer efficacy among HDACIs. Our results demonstrate that the novel HDACI CKD5 is a promising therapeutic candidate for glioblastoma.
authors.affiliation: Division of Pediatric Neurosurgery, Pediatric Clinical Neuroscience Center, Seoul National University Children's Hospital, Seoul, Korea.|Adolescent Cancer Center, Seoul National University Cancer Hospital, Seoul, Korea.
authors.forename: Seung Ah
authors.initials: SA
authors.lastname: Choi
authors.affiliation: Division of Pediatric Neurosurgery, Pediatric Clinical Neuroscience Center, Seoul National University Children's Hospital, Seoul, Korea.|Adolescent Cancer Center, Seoul National University Cancer Hospital, Seoul, Korea.
authors.forename: Pil Ae
authors.initials: PA
authors.lastname: Kwak
authors.affiliation: Department of Neurosurgery, Seoul National University Hospital, Seoul, Korea.
authors.forename: Chul-Kee
authors.initials: CK
authors.lastname: Park
authors.affiliation: Division of Pediatric Neurosurgery, Pediatric Clinical Neuroscience Center, Seoul National University Children's Hospital, Seoul, Korea.|Department of Neurosurgery, Seoul National University Hospital, Seoul, Korea.
authors.forename: Kyu-Chang
authors.initials: KC
authors.lastname: Wang
authors.affiliation: Division of Pediatric Neurosurgery, Pediatric Clinical Neuroscience Center, Seoul National University Children's Hospital, Seoul, Korea.|Adolescent Cancer Center, Seoul National University Cancer Hospital, Seoul, Korea.|Department of Neurosurgery, Seoul National University Hospital, Seoul, Korea.
authors.forename: Ji Hoon
authors.initials: JH
authors.lastname: Phi
authors.affiliation: Division of Pediatric Neurosurgery, Pediatric Clinical Neuroscience Center, Seoul National University Children's Hospital, Seoul, Korea.|Department of Neurosurgery, Seoul National University Hospital, Seoul, Korea.|Department of Anatomy, Seoul National University Hospital, Seoul, Korea.
authors.forename: Ji Yeoun
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Chong Kun Dang Research Institute, CKD Pharmaceuticals, Gyeonggi-do, Korea.
authors.forename: Chang Sik
authors.initials: CS
authors.lastname: Lee
authors.affiliation: Chong Kun Dang Research Institute, CKD Pharmaceuticals, Gyeonggi-do, Korea.
authors.forename: Ju-Hee
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Division of Pediatric Neurosurgery, Pediatric Clinical Neuroscience Center, Seoul National University Children's Hospital, Seoul, Korea.|Adolescent Cancer Center, Seoul National University Cancer Hospital, Seoul, Korea.|Department of Neurosurgery, Seoul National University Hospital, Seoul, Korea.
authors.forename: Seung-Ki
authors.initials: SK
authors.lastname: Kim
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D005909:Glioblastoma / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D013997:Time Factors; D047368:Tumor Burden / Q000187:drug effects; D014508:Urea / Q000031:analogs & derivatives* / Q000494:pharmacology; D000077337:Vorinostat; D023041:Xenograft Model Antitumor Assays
chemical_list: C000626324:CKD5 compound; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; C012589:trichostatin A; D000077337:Vorinostat; D014508:Urea
keywords: epigenetics; glioblastoma; histone deacetylase inhibitor