Gold(III) Complexes with Phenanthroline-derivatives Ligands Induce Apoptosis in Human Colorectal and Breast Cancer Cell Lines

• Published in: Journal of pharmaceutical sciences Vol. 111; no. 12; p. 3215
• Main Authors: Milutinović, Milena G, Milivojević, Nevena N, Đorđević, Nevena M, Nikodijević, Danijela D, Radisavljević, Snežana R, Đeković Kesić, Ana S, Marković, Snežana D
• Format: Journal Article
• Language: English
• Published: United States 01-12-2022
• Subjects: Apoptosis; Breast Neoplasms - drug therapy; Caspase 9 - pharmacology; Cell Line, Tumor; Colorectal Neoplasms - drug therapy; Female; Gold - chemistry; Gold - pharmacology; Humans; Ligands; Phenanthrolines - chemistry; Phenanthrolines - pharmacology; Proto-Oncogene Proteins c-bcl-2 - pharmacology; Bcl-2; Bax; Metal-based complexes; Caspases; Cell death; Anticancer activity
• ISSN: 1520-6017
• DOI: 10.1016/j.xphs.2022.09.021

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.