Araujo Nobrega, Joaquim

Azevedo Batista, Alzir

Colina-Vegas, Legna

De Wever, Olivier

Van Acker, Thibaut

Vanhaecke, Frank

English

Ghent University Academic Bibliography

  A NEW Ru(II) COMPLEX: DNA/HSA-BINDING, ANTI-MIGRATION AND BIOLOGICAL PROPERTIES IN A HUMAN BREAST TUMOR CELL LINE LEGNA COLINA-VEGAS (1),(2),(3) THIBAUT VAN ACKER (1), OLIVIER DE WEVER (3), ALZIR AZEVEDO BATISTA (2), JOAQUIM ARAUJO NOBREGA (2), FRANK VANHAECKE (1) (1): Atomic & Mass Spectrometry – A&MS research unit, Department of Chemistry, Ghent University, Campus Sterre, Krijgslaan 281-S12, B-9000 Ghent, Belgium (2): Department of Chemistry, Federal University of São Carlos, São Carlos, SP. Brazil (3): Laboratory of Experimental Cancer Research (LECR), Department of Radiation Oncology and Experimental Cancer Research, Ghent University, De Pintelaan 185, B-9000 Ghent, Belgium   ABSTRACT Breast cancer is the most common cause of cancer deaths among women worldwide. Triple-negative breast cancers (TNBC) do not express estrogen or progesterone receptors nor do they contain an amplified HER2/Neu gene and they account for about 15–20% of all breast cancers; no specific molecular targets or effective vulnerable chemotherapies have been identified so far [1]. For these reasons, new therapies to treat this dangerous disease are urgently needed [2]. A new metal complex with the formula [RuCl(CTZ)(η6-p-cymene)(PPh3)]PF6 (CTZ: clotrimazole and PPh3: triphenylphosphine) was synthesized and fully characterized. This complex presented groove-binding interaction with DNA, as supported by UV-vis titration, viscosity, circular dichroism, gel electrophoresis and Hoechst 33258 displacement assay and a spontaneous static quenching mechanism with HSA protein through electrostatic interactions. The in vitro biological screening in prostate, lung and breast tumor cell lines showed more cytotoxic effects than free ligand CTZ and the positive controls cisplatin and doxorubicin; in TNBC MDA-MB-231 cells, the complex induces morphological changes, cell cycle arrest in the sub-G1 phase, cell death by apoptosis and inhibition of colony formation and migration. In order to investigate the metal uptake in MDA-MB-231 cells, single-cell Laser Ablation-Inductively Coupled Plasma-Mass Spectrometry (LA-ICP-MS) was applied by individual ablation of cells from a monolayer exposed to the ruthenium complex for 24 h, after fixation and dehydration. The results obtained from this study demonstrated the feasibility of the strategy to coordinate a transition metal with an organic molecule with the desirable biological property -to improve the efficacy of the latter. Acknowledge: Brazilian foundations CAPES, CNPq, FAPESP (Grant #2017/23254-9)  REFERENCES  [1] Curigliano G. and Goldhirsch A., “The triple-negative subtype: new ideas for the poorest prognosis breast cancer”, J. Natl. Cancer Inst. Monogr., Vol. 2011, No. 43, (2011), pp 108-110.  [2] Biersack B., Ahmad A., Sarkar F. H. and Schobert R., “Coinage metal complexes against breast cancer”, Curr. Med. Chem., Vol. 19, No. 23, (2012), pp 3949-3956.    

A new Ru(II) complex : DNA/HSA-binding, anti-migration and biological properties in a human breast tumor cell line

https://biblio.ugent.be/publication/8572051/file/8572052

A new Ru(II) complex : DNA/HSA-binding, anti-migration and biological properties in a human breast tumor cell line

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