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dc.contributor.authorPark, Kyung Chan
dc.contributor.authorFouani, Leyla
dc.contributor.authorJansson, Patric J
dc.contributor.authorWooi, Danson
dc.contributor.authorSahni, Sumit
dc.contributor.authorLane, Darius JR
dc.contributor.authorPalanimuthu, Duraippandi
dc.contributor.authorLok, Hiu Chuen
dc.contributor.authorKovacevic, Zaklina
dc.contributor.authorHuang, Michael LH
dc.contributor.authorKalinowski, Danuta S
dc.contributor.authorRichardson, Des R
dc.date.accessioned2021-09-22T04:26:03Z
dc.date.available2021-09-22T04:26:03Z
dc.date.issued2016
dc.identifier.issn1756-5901
dc.identifier.doi10.1039/c6mt00105j
dc.identifier.urihttp://hdl.handle.net/10072/408203
dc.description.abstractCopper is an essential trace metal required by organisms to perform a number of important biological processes. Copper readily cycles between its reduced Cu(i) and oxidised Cu(ii) states, which makes it redox active in biological systems. This redox-cycling propensity is vital for copper to act as a catalytic co-factor in enzymes. While copper is essential for normal physiology, enhanced copper levels in tumours leads to cancer progression. In particular, the stimulatory effect of copper on angiogenesis has been established in the last several decades. Additionally, it has been demonstrated that copper affects tumour growth and promotes metastasis. Based on the effects of copper on cancer progression, chelators that bind copper have been developed as anti-cancer agents. In fact, a novel class of thiosemicarbazone compounds, namely the di-2-pyridylketone thiosemicarbazones that bind copper, have shown great promise in terms of their anti-cancer activity. These agents have a unique mechanism of action, in which they form redox-active complexes with copper in the lysosomes of cancer cells. Furthermore, these agents are able to overcome P-glycoprotein (P-gp) mediated multi-drug resistance (MDR) and act as potent anti-oncogenic agents through their ability to up-regulate the metastasis suppressor protein, N-myc downstream regulated gene-1 (NDRG1). This review provides an overview of the metabolism and regulation of copper in normal physiology, followed by a discussion of the dysregulation of copper homeostasis in cancer and the effects of copper on cancer progression. Finally, recent advances in our understanding of the mechanisms of action of anti-cancer agents targeting copper are discussed.
dc.languageEnglish
dc.publisherROYAL SOC CHEMISTRY
dc.relation.ispartofpagefrom874
dc.relation.ispartofpageto886
dc.relation.ispartofissue9
dc.relation.ispartofjournalMetallomics
dc.relation.ispartofvolume8
dc.subject.fieldofresearchChemical sciences
dc.subject.fieldofresearchcode34
dc.subject.keywordsScience & Technology
dc.subject.keywordsLife Sciences & Biomedicine
dc.subject.keywordsBiochemistry & Molecular Biology
dc.subject.keywordsDownstream-Regulated Gene-1
dc.subject.keywordsEpithelial-Mesenchymal Transition
dc.titleCopper and conquer: copper complexes of di-2-pyridylketone thiosemicarbazones as novel anti-cancer therapeutics
dc.typeJournal article
dcterms.bibliographicCitationPark, KC; Fouani, L; Jansson, PJ; Wooi, D; Sahni, S; Lane, DJR; Palanimuthu, D; Lok, HC; Kovacevic, Z; Huang, MLH; Kalinowski, DS; Richardson, DR, Copper and conquer: copper complexes of di-2-pyridylketone thiosemicarbazones as novel anti-cancer therapeutics, Metallomics, 2016, 8 (9), pp. 874-886
dc.date.updated2021-09-22T04:24:09Z
gro.hasfulltextNo Full Text
gro.griffith.authorRichardson, Des R.


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