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pmid:32902006
An Organometallic Gold(I) Bis-N-Heterocyclic Carbene Complex with Multimodal Activity in Ovarian Cancer Cells.
Samuel M Meier-Menches · Benjamin Neuditschko · Katja Zappe · Martin Schaier · Marlene C Gerner · Klaus G Schmetterer · Giorgia Del Favero · Riccardo Bonsignore · Margit Cichna-Markl · Gunda Koellensperger · Angela Casini · Christopher Gerner
Chemistry (Weinheim an der Bergstrasse, Germany) · 2020 doi:10.1002/chem.202003495
Paper
complete
Experiment
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Data
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Analysis
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Execution
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Complete file
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This study sheds light on the molecular reactivity and mode of action of AuTMX2 in the cellular context using mass spectrometry-based methods, including shotgun proteomics in A2780 ovarian cancer cells. In contrast to other metal-based anticancer agents, this organogold compound is less prone to form coordinative bonds with biological nucleophiles and is expected to exert its drug effects mainly by non-covalent interactions. Global protein expression changes of treated cancer cells revealed a multimodal mode of action of AuTMX2 by alterations in the nucleolus, telomeres, actin stress-fibres and stress-responses, which were further supported by pharmacological assays, fluorescence microscopy and cellular accumulation experiments. 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