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dc.contributor.authorVittorio, O
dc.contributor.authorBrandl, M
dc.contributor.authorCirillo, G
dc.contributor.authorKimpton, K
dc.contributor.authorHinde, E
dc.contributor.authorGaus, K
dc.contributor.authorYee, E
dc.contributor.authorKumar, N
dc.contributor.authorDuong, H
dc.contributor.authorFleming, C
dc.contributor.authorHaber, M
dc.contributor.authorNorris, M
dc.contributor.authorBoyer, C
dc.contributor.authorKavallaris, M
dc.date.accessioned2020-12-21T02:15:27Z
dc.date.available2020-12-21T02:15:27Z
dc.date.issued2016-07-26
dc.identifierpii: 10201
dc.identifier.citationVittorio, O., Brandl, M., Cirillo, G., Kimpton, K., Hinde, E., Gaus, K., Yee, E., Kumar, N., Duong, H., Fleming, C., Haber, M., Norris, M., Boyer, C. & Kavallaris, M. (2016). Dextran-Catechin: An anticancer chemically-modified natural compound targeting copper that attenuates neuroblastoma growth.. Oncotarget, 7 (30), pp.47479-47493. https://doi.org/10.18632/oncotarget.10201.
dc.identifier.issn1949-2553
dc.identifier.urihttp://hdl.handle.net/11343/256848
dc.description.abstractNeuroblastoma is frequently diagnosed at advanced stage disease and treatment includes high dose chemotherapy and surgery. Despite the use of aggressive therapy survival rates are poor and children that survive their disease experience long term side effects from their treatment, highlighting the need for effective and less toxic therapies. Catechin is a natural polyphenol with anti-cancer properties and limited side effects, however its mechanism of action is unknown. Here we report that Dextran-Catechin, a conjugated form of catechin that increases serum stability, is preferentially and markedly active against neuroblastoma cells having high levels of intracellular copper, without affecting non-malignant cells. Copper transporter 1 (CTR1) is the main transporter of copper in mammalian cells and it is upregulated in neuroblastoma. Functional studies showed that depletion of CTR1 expression reduced intracellular copper levels and led to a decrease in neuroblastoma cell sensitivity to Dextran-Catechin, implicating copper in the activity of this compound. Mechanistically, Dextran-Catechin was found to react with copper, inducing oxidative stress and decreasing glutathione levels, an intracellular antioxidant and regulator of copper homeostasis. In vivo, Dextran-Catechin significantly attenuated tumour growth in human xenograft and syngeneic models of neuroblastoma. Thus, Dextran-Catechin targets copper, inhibits tumour growth, and may be valuable in the treatment of aggressive neuroblastoma and other cancers dependent on copper for their growth.
dc.languageeng
dc.publisherImpact Journals, LLC
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleDextran-Catechin: An anticancer chemically-modified natural compound targeting copper that attenuates neuroblastoma growth.
dc.typeJournal Article
dc.identifier.doi10.18632/oncotarget.10201
melbourne.affiliation.departmentSchool of Physics
melbourne.source.titleOncotarget
melbourne.source.volume7
melbourne.source.issue30
melbourne.source.pages47479-47493
dc.rights.licenseCC BY
melbourne.elementsid1234115
melbourne.openaccess.pmchttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC5216955
melbourne.contributor.authorHinde, Elizabeth
dc.identifier.eissn1949-2553
melbourne.accessrightsOpen Access


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