Silver(I) complexes containing diclofenac and niflumic acid induce apoptosis in human-derived cancer cell lines

Abstract

We investigated the anti-cancer activity of [Ag(μ-dicl)]_n 1 and [AgH(nif)₂] 2 complexes against human cancer cell lines (MCF-7, HT-29, and HepG2) and mouse fibroblast (3T3-L1) cell line. Anti-proliferative activity was monitored by XTT cell viability and LDH leakage assays. Cell death mode was evaluated by multi-caspase activity, annexin V cytofluorimetric, MMP, cell cycle arrest, and ROS generation assays. Antioxidant capacity was evaluated on SOD, GPx, GR, and CAT enzymes. The XTT and LDH assay results showed that both complexes exhibited strong cytotoxicity against the tested cancer cell lines. The apoptotic mechanisms of the complexes were demonstrated by loss of MMP and increase in phosphatidylserine translocation, sub-G1 phase, and multi-caspase activity. Besides, both complexes induced the oxidative stress in MCF-7 cells by decreasing the activity of GPx, GR, and CAT enzymes. In conclusion, both Ag(I) complexes, especially 1, warrant for further in vivo evaluation as a new alternative in cancer treatment.

Highlights

• Ag(I) complexes inhibited cell proliferation and induced LDH leakage in human cancer cell lines.

• Ag(I) complexes induced apoptosis through MMP disruption and ROS generation.

• Ag(I) complexes mimicked the multi-caspase activity.

• Ag(I) complexes increased the accumulation of sub-G1 phase.

• Ag(I) complexes inhibited the activity of antioxidant system enzymes.

Keywords:

• Silver(I) complexes
• cytotoxicity
• cell cycle
• apoptosis
• enzyme activity

Disclosure statement

The authors declare that there is no conflict of interest with respect to the research, authorship, and/or publication of this article.

Author contributions

Conceived and designed the experiments: AA, SC (group leader). Performed the experiments: AA, SC, and BC. Analysed the data: AA, SC, and BC. Contributed reagents/materials/analysis tools: AA, SC, and BC. Wrote the article: AA, SC, and BC. All authors read and approved the final manuscript.