- Induction of Necroptosis in Cancer Stem Cells using a Nickel(II)-Dithiocarbamate Phenanthroline Complex
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The cytotoxic properties of a series of nickel(II)-dithiocarbamate phenanthroline complexes is reported. The complexes 1–6 kill bulk cancer cells and cancer stem cells (CSCs) with micromolar potency. Two of the complexes, 2 and 6, kill twice as many breast cancer stem cell (CSC)-enriched HMLER-shEcad cells as compared to breast CSC-depleted HMLER cells. Complex 2 inhibits mammosphere formation to a similar extent as salinomycin (a CSC-specific toxin). Detailed mechanistic studies suggest that 2 induces CSC death by necroptosis, a programmed form of necrosis. Specifically, 2 triggers MLKL phosphorylation, oligomerization, and translocation to the cell membrane. Additionally, 2 induces necrosome-mediated propidium iodide (PI) uptake and mitochondrial membrane depolarisation, as well as morphological changes consistent with necroptotosis. Strikingly, 2 does not evoke necroptosis by intracellular reactive oxygen species (ROS) production or poly(ADP) ribose polymerase (PARP-1) activation.
- Flamme, Marie,Cressey, Paul B.,Lu, Chunxin,Bruno, Peter M.,Eskandari, Arvin,Hemann, Michael T.,Hogarth, Graeme,Suntharalingam, Kogularamanan
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p. 9674 - 9682
(2017/07/22)
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- THE DIRECT ELECTROCHEMICAL SYNTHESIS OF DIALKYLDITHIOCARBAMATE AND DIETHYLDITHIOPHOSPHATE COMPLEXES OF MAIN GROUP AND TRANSITION METALS
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Dialkyldithiocarbamate derivatives (R2NCS2)nM of a number of metals (M=Fe, Co, Ni, Cu, Ag, Zn, Cd, In, Tl) have been synthesised in good yield by electrochemical oxidation of appropriate sacrificial anodes in non-aqueous solutions of either the corresponding tetraalkylthiuran disulphide (R2NCS2)2 (R=Me, Et) or a mixture of carbon disulphide plus the secondary amine R2NH (R=Et, i-Pr; R2NH=piperidine).Similar experiments with solutions of (EtO)2P(S)SH (=HL) gave MLn* derivatives (M=Fe, Co, Ni, Cu, Ag, Au, Zn, Cd, Hg, Ga, In, Tl) while in the presence of HL+1,10-phenanthroline, MLn.phen derivatives were obtained for M=V, Mn, Fe, Co, Zn, and Ga.
- Geloso, Corrado,Kumar, Rajesh,Lopez-Grado, Jaime Romero,Tuck, Dennis G.
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p. 928 - 932
(2007/10/02)
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