Due to their promising effects, gold(III) complexes recently drew increasing attention in the design of new metal-based anticancer therapeutics. Two gold(III) complexes, square-planar Au(DPP)Cl2+ - ...Complex 1 and distorted square-pyramidal Au(DMP)Cl3 - Complex 2 (where DPP=4,7-diphenyl-1,10-phenanthroline and DMP=2,9-dimethyl-1,10-phenanthroline) were previously synthetized, described and approved as complexes with pronounced cytotoxic effects on colorectal HCT-116 and breast MDA-MB-231 cancer cells. This study investigated the type of cell death by AO/EB double staining, and identification of possible targets responsible for their cytotoxicity, monitored by immunofluorescence and qPCR methods. Both complexes induced apoptosis in all applied concentrations. In the HCT-116 cells apoptosis was activated by external apoptotic pathway, via increase of Fas receptor protein expression and Caspase 8 gene expression. Also, the mitochondrial pathway was triggered by affecting the Bcl-2 members of regulatory proteins and increased caspase 9 protein expression. In MDA-MB-231 cells, apoptosis was initiated from the mitochondria, due to disbalance between expressions of pro- and anti-apoptotic Bcl-2 family members and caspase 9 activation. Complex 1 shows better activity compared to Complex 2, which is in accordance with its structural characteristics. The results deal weighty data about proapoptotic activity of gold(III) complexes and highlighted potential targets for cancer therapy.
Kinetics of the substitution reactions between monofunctional Au(III) complexes, Au(dien)Cl
2+
, Au(bpma)Cl
2+
and Au(terpy)Cl
2+
(dien = 3-azapentane-1,5-diamine, bpma = di-(2-picolyl) amine, terpy ...= 2,2′;6′,2″-terpyridine), and biologically relevant sulphur ligands, namely glutathione (GSH),
l
-methionine (
l
-Met) and
l
-cysteine (
l
-Cys), were studied in 0.1 M HCl (pH = 1.0). The reactions were followed under
pseudo
-first-order conditions as a function of ligand concentration and temperature using stopped-flow spectrophotometry. The Au(terpy)Cl
2+
complex proved to be more reactive than the Au(bpma)Cl
2+
and Au(dien)Cl
2+
complexes. The reactivities of the nucleophiles follow the same order for all three complexes, viz.
l
-Met > GSH >
l
-Cys. Values of the activation parameters of the reactions support an associative substitution mechanism. In order to confirm that these monofunctional Au(III) complexes undergo a single substitution process in strongly acidic medium, the reaction between Au(terpy)Cl
2+
and
l
-Met was studied by HPLC. At pH = 1.0, only one reaction product was detected.
