The dietary flavonoid isoliquiritigenin is a potent cytotoxin for human neuroblastoma cells

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dc.contributor.authorAlshangiti, Amnah M.
dc.contributor.authorTogher, Katie L.
dc.contributor.authorHegarty, Shane V.
dc.contributor.authorSullivan, Aideen M.
dc.contributor.authorO'Keeffe, Gerard W.
dc.contributor.funderScience Foundation Irelanden
dc.contributor.funderGovernment of Saudi Arabiaen
dc.date.accessioned2019-11-19T12:01:52Z
dc.date.available2019-11-19T12:01:52Z
dc.date.issued2019-01-30
dc.description.abstractNeuroblastoma (NB) is the most common extracranial solid tumor of early childhood; it accounts for approximately 8–10% of all childhood cancers and is the most common cancer in children in the first year of life. Patients in the high-risk group have a poor prognosis, with relapses being common and often refractory to drug treatment in those that survive. Moreover, the drug treatment itself can lead to a range of long-term sequelae. Therefore, there is a critical need to identify new therapeutics for NB. Isoliquiritigenin (ISLQ) is a naturally-occurring, dietary chalcone-type flavonoid with a range of biological effects that depend on the cell type and context. ISLQ has potential as an anticancer agent. Here we show that ISLQ has potent cytotoxic effects on SK-N-BE(2) and IMR-32 human NB cells, which carry amplification of the MYCN gene, the main prognostic marker of poor survival in NB. ISLQ was found to increase cellular reactive oxygen species (ROS). The cytotoxic effect of ISLQ was blocked by small molecule inhibitors of oxidative stress-induced cell death, and by the antioxidant N-acetyl-l-cysteine (NAC). Combined treatment of either SK-N-B-E(2) or IMR-32 cells with ISLQ and the anticancer agent cisplatin resulted in loss of cell viability that was greater than that induced by cisplatin alone. This study provides proof-of-principle that ISLQ is a potent cytotoxin for MYCN-amplified human NB cells. This is an important first step in rationalizing the further study of ISLQ as a potential adjunct therapy for high-risk NB.en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.articleidNS20180201en
dc.identifier.citationAlshangiti, A., Togher, K., Hegarty, S.V., Sullivan, A.M. and O'Keeffe, G.W., 2019. The dietary flavonoid isoliquiritigenin is a potent cytotoxin for human neuroblastoma cells. Neuronal Signaling, (NS20180201). DOI:10.1042/NS20180201en
dc.identifier.doi10.1042/NS20180201en
dc.identifier.eissn2059-6553
dc.identifier.endpage13en
dc.identifier.issued1en
dc.identifier.journaltitleNeuronal Signalingen
dc.identifier.startpage1en
dc.identifier.urihttps://hdl.handle.net/10468/9073
dc.identifier.volume3en
dc.language.isoenen
dc.publisherPortland Pressen
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/SFI Career Development Award/15/CDA/3498/IE/Development of GDF5 neurotrophic factor therapy for Parkinson_s disease./en
dc.relation.urihttp://www.neuronalsignaling.org/content/3/1/NS20180201
dc.rights© 2019 The Author(s)en
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subjectNeuroblastoma (NB)en
dc.subjectEarly childhooden
dc.subjectChildhood canceren
dc.subjectTherapeuticsen
dc.subject~Anatomy and Neuroscience - Journal Articles~en
dc.titleThe dietary flavonoid isoliquiritigenin is a potent cytotoxin for human neuroblastoma cellsen
dc.typeArticle (peer-reviewed)en
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