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01.01.2012 | Laboratory Investigation - Human/Animal Tissue

Norcantharidin impairs medulloblastoma growth by inhibition of Wnt/β-catenin signaling

verfasst von: Flora Cimmino, Maria Nunzia Scoppettuolo, Marianeve Carotenuto, Pasqualino De Antonellis, Valeria Di Dato, Gennaro De Vita, Massimo Zollo

Erschienen in: Journal of Neuro-Oncology | Ausgabe 1/2012

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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.

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Titel: Norcantharidin impairs medulloblastoma growth by inhibition of Wnt/β-catenin signaling
verfasst von: Flora Cimmino
Maria Nunzia Scoppettuolo
Marianeve Carotenuto
Pasqualino De Antonellis
Valeria Di Dato
Gennaro De Vita
Massimo Zollo
Publikationsdatum: 01.01.2012
Verlag: Springer US
Erschienen in: Journal of Neuro-Oncology / Ausgabe 1/2012
Print ISSN: 0167-594X
Elektronische ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-011-0645-y

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