Comparative Antitumor Efficacy and Toxicity Profile of SCC5, An Ag(I) N-Heterocyclic Carbene Complex, Relative to Platinum-based Chemotherapeutics.

Abstract

Background/aim: Platinum-based chemotherapeutics remain the standard of care for many solid tumors; however, they have dose-limiting toxicities. Silver(I) N-heterocyclic carbene complexes represent a novel class of metallodrugs with potential anticancer activity and improved tolerability. This study evaluated SCC5, a silver(I) acetate complex derived from 1,3-dimethyl-4,5-dichloroimidazole-2-ylidene, across a panel of human cancer cell lines and in vivo toxicity models. Mechanistic analysis of apoptosis was also performed using caspase-8 immunoblotting.

Materials and methods: Eight human cancer cell lines (melanoma, colon, renal, bladder, ovarian, and prostate) were treated with SCC5 and three FDA-approved platinum drugs (cisplatin, carboplatin, oxaliplatin). Antiproliferative activity was measured using the sulforhodamine B assay. In vivo toxicity was assessed in CD-1 mice receiving escalating intraperitoneal doses (10-50 mg/kg), with survival monitored over 21 days. Caspase-8 was analyzed by western blotting in SCC5-treated HT-29 cells.

Results: SCC5 exhibited half-maximal inhibitory doses ranging from 10 to 30 μM, comparable to carboplatin and was slightly less potent than cisplatin and oxaliplatin. However, SCC5 demonstrated superior safety, with 100% survival at doses that were lethal to platinum compounds, supporting its more favorable therapeutic index. Western blot analysis revealed dose- and time-dependent loss of caspase-8 expression following SCC5 treatment, suggesting activation of apoptosis-related pathways.

Conclusion: SCC5 maintains broad-spectrum antiproliferative activity with markedly improved in vivo tolerability compared to platinum drugs. These findings support continued preclinical development of SCC5 as a novel silver-based chemotherapeutic.