title: Norcantharidin impairs medulloblastoma growth by inhibition of Wnt/β-catenin signaling.
abstract: Medulloblastoma is one of the leading causes of morbidity and mortality in pediatric cancer. Wnt-active tumors, an independent molecular subgroup in medulloblastoma, are characterized by a distinct pattern of genomic aberrations. We assessed the anticancer activity of cantharidin and norcantharidin against medulloblastoma, as cell lines in vitro and in athymic nude mice in vivo. Cantharidin and norcantharidin treatment impaired the growth of DAOY and UW228 medulloblastoma cells and promoted the loss of β-catenin activation and the β-catenin nuclearization linked to N-cadherin impairment in vitro. Intra-peritoneal administration of norcantharidin inhibited the growth of intra-cerebellum tumors in orthotopic xenograft nude mice. Analysis of the xenograft tissues revealed enhanced neuronal differentiation and reduced β-catenin expression. Our findings suggest that norcantharidin has potential therapeutic applications in the treatment of medulloblastoma as a result of its ability to cross the blood-brain barrier and its impairment of Wnt-β-catenin signaling.
authors: CEINGE, Centro di Ingegneria Genetica, Biotecnologie Avanzate, Via Gaetano Salvatore 486, 80145 Naples, Italy.
authors: Flora
authors: F
authors: Cimmino
authors: Maria Nunzia
authors: MN
authors: Scoppettuolo
authors: Marianeve
authors: M
authors: Carotenuto
authors: Pasqualino
authors: P
authors: De Antonellis
authors: Valeria Di
authors: VD
authors: Dato
authors: Gennaro
authors: G
authors: De Vita
authors: Massimo
authors: M
authors: Zollo
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000502:physiology; D001812:Blood-Brain Barrier / Q000502:physiology; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology*; D002453:Cell Cycle / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D016195:G2 Phase / Q000187:drug effects; D017930:Genes, Reporter; D007202:Indicators and Reagents; D008156:Luciferases / Q000235:genetics; D008527:Medulloblastoma / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation / Q000502:physiology; D016133:Polymerase Chain Reaction; D021381:Protein Transport / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D051153:Wnt Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D051176:beta Catenin / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: D000970:Antineoplastic Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D007202:Indicators and Reagents; D051153:Wnt Proteins; D051176:beta Catenin; C069741:norcantharidin; D008156:Luciferases