Highly cytotoxic gold(i)-phosphane dithiocarbamate complexes trigger an ER stress-dependent immune response in ovarian cancer cells

Abstract

Highly cytotoxic AuI-dithiocarbamate complexes were designed to induce severe integrative stress in ovarian cancer cells, leading to the surface exposure of calreticulin, which is a first step in the activation of immune system.

A novel cyclic dinuclear gold(i) complex induces anticancer activity via an oxidative stress-mediated intrinsic apoptotic pathway in MDA-MB-231 cancer cells

“…1,15,16,20 These studies stimulated the development of a wide variety of the linear gold(I)-phosphane complexes that display significant antiproliferative effects. 4,[7][8][9][10][21][22][23][24][25][26][27][28][29][30][31][32][33] Along with the linear gold(I) compounds, the tetrahedral chelated gold(I)-diphosphane cationic complexes have also been recognized as effective cytotoxic agents. 2,3,34,35 It has been demonstrated that the increased lipophilicity of the complexes significantly enhances their cellular accumulation, bioavailability and hence their antitumor activity.…”

Combined Effect of Caspase-Dependent and Caspase-Independent Apoptosis in the Anticancer Activity of Gold Complexes with Phosphine and Benzimidazole Derivatives

“…In the present study, the results obtained in the caspase-3 assay and in the determination of ROS production indicate that gold complexes could have antitumor behavior, being able to induce apoptotic cell death through the increase of ROS levels. The redox potentials of 1 and 2 are outside the biologically accessible redox potential window of −0.4 to +0.8 V, suggesting that these complexes do not directly generate ROS due to the Au(I)/Au(III) process but rather as a consequence of inhibition of TrxR [48]. This inhibition damages the thioredoxin system, an important cellular antioxidant defense, increasing ROS levels, and leading to cell death [51][52][53].…”

“…Elevated ROS causes mitochondrial membrane depolarization, which produces a disruption of the electron transport chain, leading to the release of cytochrome c and the apoptosis-inducing factor (AIF) from the mitochondria. Cytochrome c release induces caspase-dependent apoptosis, mediated by caspase-3 and caspase-9 activation, whilst AIF is translocated to the nucleus and produces caspase-independent apoptosis [48].…”

“…In the case of gold complexes, previous studies have reported that this class of compounds can also induce apoptosis through both caspase-dependent and caspaseindependent mechanisms [48,49]. In this context, the effect of complexes 1 and 2 on caspase-3 activity was analyzed.…”

“…Previously published studies [48,49] stated that Au(I) and Au(III) complexes produce cell death through the induction of oxidative stress. Therefore, the effect of compounds on ROS production was analyzed.…”