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

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.

Effects of trans‑(±)‑kusunokinin on chemosensitive and chemoresistant ovarian cancer cells

“…This effect may be due to apoptosis occurring during the experimental process. These results were previously reported ( 47 – 49 ). Therefore, measurements of multi-caspase activity in non-treated cells at 24, 48 and 72 h were performed, which served as an internal control to assess the function of trans-(±)-kusunokinin on multi-caspase activity at 72 h ( Fig.…”

Recent development of gold(i) and gold(iii) complexes as therapeutic agents for cancer diseases

“…The findings suggest that the gold(III) complex 285 exhibited a remarkable degree of pro-apoptotic effects, and that TrxR inhibition is associated with oxidative stress and mitochondrial dysfunction in A2780 cells. 217 In 2017, Pantelic ´et al synthesized six gold(III) complexes 288a-f containing cyclohexyl-functionalized ethylenediamine-N,N 0 -diacetate. MTT assay was used to test these gold complexes with cancer cell lines such as human melanoma Fem-x, human colon cancer LS174T, non-small cell lung cancer A549, and non-cancerous human embryonic lung cell MRC-5.…”

“…The findings suggest that the gold( iii ) complex 285 exhibited a remarkable degree of pro-apoptotic effects, and that TrxR inhibition is associated with oxidative stress and mitochondrial dysfunction in A2780 cells. 217…”

In Vitro Anti-SARS-CoV-2 Activity of Selected Metal Compounds and Potential Molecular Basis for Their Actions Based on Computational Study

“…These compounds are of different origins: some are commercially available, others were previously prepared and characterized. A few, e.g., Auranofin, NAMI-A, KP1019, TiCp 2 Cl 2, are clinically established or have entered clinical trials [ 6 , 26 , 27 , 28 , 29 , 30 ].…”

“…Auranofin and SbCl 3 were supplied by Merck (codes A6733 and 215783, respectively; purity ≥ 98%). The iodo-analogue of Auranofin, AuL12, AuOXO6, Aubipyc, NAMI-A, KP1019, and TiCp 2 Cl 2 were synthesized as reported in the literature with a purity ≥ 95% [ 6 , 26 , 27 , 28 , 29 , 30 ].…”