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Biomedicines
Volume 9
Issue 8
10.3390/biomedicines9080871
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Article

Au2phen and Auoxo6, Two Dinuclear Oxo-Bridged Gold(III) Compounds, Induce Apoptotic Signaling in Human Ovarian A2780 Cancer Cells

by
Giulia Gorini
1,
Francesca Magherini
1,
Tania Fiaschi
1,
Lara Massai
2,
Matteo Becatti
1,
Alessandra Modesti
1,
Luigi Messori
2,* and
Tania Gamberi
1,*
1
Department of Experimental and Clinical Biomedical Sciences, University of Florence, Viale Morgagni 50, 50134 Firenze, Italy
2
Department of Chemistry ‘Ugo Schiff’, University of Florence, via della Lastruccia 3-13, Sesto Fiorentino, 50019 Firenze, Italy
*
Authors to whom correspondence should be addressed.
Biomedicines 2021, 9(8), 871; https://doi.org/10.3390/biomedicines9080871
Submission received: 31 May 2021 / Revised: 18 July 2021 / Accepted: 19 July 2021 / Published: 23 July 2021
(This article belongs to the Special Issue Metal-Based Complexes in Cancer Treatment)
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Abstract

Au2phen ((2,9-dimethyl-1,10-phenanthroline)2Au2(µ-O)2)(PF6)2 and Auoxo6 ((6,6′-dimethyl-2,2′-bipyridine)2Au2(µ-O)2)(PF6)2 are two structurally related gold(III) complexes that were previously reported to display relevant and promising anticancer properties in vitro toward a large number of human cancer cell lines. To expand the knowledge on the molecular mechanisms through which these gold(III) complexes trigger apoptosis in cancer cells, further studies have been performed using A2780 ovarian cancer cells as reference models. For comparative purposes, parallel studies were carried out on the gold(III) complex AuL12 (dibromo(ethylsarcosinedithiocarbamate)gold(III)), whose proapoptotic profile had been earlier characterized in several cancer cell lines. Our results pointed out that all these gold(III) compounds manifest a significant degree of similarity in their cellular and proapoptotic effects; the main observed perturbations consist of potent thioredoxin reductase inhibition, disruption of the cell redox balance, impairment of the mitochondrial membrane potential, and induction of associated metabolic changes. In addition, evidence was gained of the remarkable contribution of ASK1 (apoptosis-signal-regulating kinase-1) and AKT pathways to gold(III)-induced apoptotic signaling. Overall, the observed effects may be traced back to gold(III) reduction and subsequent formation and release of gold(I) species that are able to bind and inhibit several enzymes responsible for the intracellular redox homeostasis, in particular the selenoenzyme thioredoxin reductase.
Keywords: gold(III)-based compounds; thioredoxin reductase; mitochondria; apoptosis signal pathway; A2780 ovarian cancer cells gold(III)-based compounds; thioredoxin reductase; mitochondria; apoptosis signal pathway; A2780 ovarian cancer cells

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MDPI and ACS Style

Gorini, G.; Magherini, F.; Fiaschi, T.; Massai, L.; Becatti, M.; Modesti, A.; Messori, L.; Gamberi, T. Au2phen and Auoxo6, Two Dinuclear Oxo-Bridged Gold(III) Compounds, Induce Apoptotic Signaling in Human Ovarian A2780 Cancer Cells. Biomedicines 2021, 9, 871. https://doi.org/10.3390/biomedicines9080871

AMA Style

Gorini G, Magherini F, Fiaschi T, Massai L, Becatti M, Modesti A, Messori L, Gamberi T. Au2phen and Auoxo6, Two Dinuclear Oxo-Bridged Gold(III) Compounds, Induce Apoptotic Signaling in Human Ovarian A2780 Cancer Cells. Biomedicines. 2021; 9(8):871. https://doi.org/10.3390/biomedicines9080871

Chicago/Turabian Style

Gorini, Giulia, Francesca Magherini, Tania Fiaschi, Lara Massai, Matteo Becatti, Alessandra Modesti, Luigi Messori, and Tania Gamberi. 2021. "Au2phen and Auoxo6, Two Dinuclear Oxo-Bridged Gold(III) Compounds, Induce Apoptotic Signaling in Human Ovarian A2780 Cancer Cells" Biomedicines 9, no. 8: 871. https://doi.org/10.3390/biomedicines9080871

APA Style

Gorini, G., Magherini, F., Fiaschi, T., Massai, L., Becatti, M., Modesti, A., Messori, L., & Gamberi, T. (2021). Au2phen and Auoxo6, Two Dinuclear Oxo-Bridged Gold(III) Compounds, Induce Apoptotic Signaling in Human Ovarian A2780 Cancer Cells. Biomedicines, 9(8), 871. https://doi.org/10.3390/biomedicines9080871

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