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- W2023940030 abstract "A stable gold(III)–phosphine complex [(C⁁N⁁C)2Au2(μ-dppp)](CF3SO3)2 [Au3, HC⁁N⁁CH = 2,6-diphenylpyridine; dppp = bis(diphenylphosphino)propane] displays potent in vitro cytotoxicity towards various cancers with sub-micromolar range cytotoxic IC50 values, and is significantly more potent than its structural and iso-electronic platinum(II) analog [(C⁁N⁁N)2Pt2(μ-dppp)](CF3SO3)2 (HC⁁N⁁N = 6-phenyl-2,2′-bipyridine) and gold(III)–carbene complexes. Complex Au3 displays promising inhibition on tumor growth in animal models, and its acute and sub-chronic toxicities have been examined in mice and beagle dogs. Transcriptomic and connectivity map analyses have revealed that the transcriptional profile of Au3 is similar to those of inhibitors of thioredoxin reductase (TrxR) and inducers of endoplasmic reticulum (ER) stress. As we found that Au3 is also a nanomolar inhibitor of TrxR, a model of ER stress-induced cell death mediated by inhibition of TrxR is proposed. The transcriptomic analysis also leads to the identification of TRAIL, a ligand for death receptor 5 (DR5), as a synergistic agent of the anti-tumor activity of Au3. Collectively, our results demonstrate that the gold(III) complex Au3 effectively inhibits tumor growth in vivo, and displays promising cytotoxicity towards cancer cells in association with the inhibition of TrxR, induction of ER stress and also a death-receptor-dependent apoptotic pathway." @default.
- W2023940030 created "2016-06-24" @default.
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- W2023940030 date "2013-01-01" @default.
- W2023940030 modified "2023-10-02" @default.
- W2023940030 title "A dinuclear cyclometalated gold(iii)–phosphine complex targeting thioredoxin reductase inhibits hepatocellular carcinoma in vivo" @default.
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- W2023940030 doi "https://doi.org/10.1039/c3sc21972k" @default.
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