An Organometallic Gold(I) Bis-N-Heterocyclic Carbene Complex with Multimodal Activity in Ovarian Cancer Cells
- Author(s)
- 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
- Abstract
The organometallic Au-I 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 spectrometrybased 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.
- Organisation(s)
- Department of Analytical Chemistry, Department of Inorganic Chemistry, Core Facility Multimodal Imaging, Department of Food Chemistry and Toxicology, Joint Metabolome Facility
- External organisation(s)
- Technische Universität München, Medizinische Universität Wien
- Journal
- Chemistry: A European Journal
- Volume
- 26
- Pages
- 15528-15537
- No. of pages
- 10
- ISSN
- 0947-6539
- DOI
- https://doi.org/10.1002/chem.202003495
- Publication date
- 12-2020
- Peer reviewed
- Yes
- Austrian Fields of Science 2012
- 104003 Inorganic chemistry, 104015 Organic chemistry, 301904 Cancer research
- Keywords
- ASJC Scopus subject areas
- Catalysis, Organic Chemistry
- Sustainable Development Goals
- SDG 3 - Good Health and Well-being
- Portal url
- https://ucrisportal.univie.ac.at/en/publications/e955e7e1-51d0-4f52-b95b-701acca1029e