An Organometallic Gold(I) Bis-N-Heterocyclic Carbene Complex with Multimodal Activity in Ovarian Cancer Cells
- Authors: Meier-Menches S.M.; Neuditschko B.; Zappe K.; Schaier M.; Gerner M.C.; Schmetterer K.G.; Del Favero G.; Bonsignore R.; Cichna-Markl M.; Koellensperger G.; Casini A.; Gerner C.
- Publication year: 2020
- Type: Articolo in rivista
- OA Link: http://hdl.handle.net/10447/576773
Abstract
The organometallic AuI bis-N-heterocyclic carbene complex [Au(9-methylcaffeine-8-ylidene)2]+ (AuTMX2) was previously shown to selectively and potently stabilise telomeric DNA G-quadruplex (G4) structures. 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. Proteomic data are available via ProteomeXchange with identifier PXD020560.