A Ru(II) Polypyridyl Complex Bearing Bathocuproine Ligand is a Potent Chemotherapeutic Agent Against Chemically Induced Skin Cancer Model

Abstract

Ruthenium‐based compounds have emerged as prospective chemotherapeutic candidates with various mechanisms of action and minimal associated side effects compared to conventional metal‐based chemotherapeutics. The present study explores the chemotherapeutic potential of [Ru(bpy)2BC]Cl2 (where bpy = 2,2′‐bipyridine and BC = bathocuproine) or RuBC on a 7,12‐dimethylbenz[a]anthracene/12‐o‐tetradecanoylphorbol‐13‐acetate (DMBA/TPA) murine skin carcinogenesis model. RuBC is well tolerated up to 2.5 mg kg−1; no changes in body weight, behavior or serum biochemistry are observed. Following IP injections, the bioavailability of the complex is high in the plasma, which favors its accumulation in the organs. Efficacy studies demonstrated that RuBC has a significant anticancer activity by week 7 of treatment and a decrease in tumor size is observed by week 6 in all tested groups. Based on western blot analyses, apoptosis through the intrinsic pathway is suggested as the main mechanism of cell death. A downregulation of the MAPK pathway is also observed. The results indicate that RuBC is a multi‐mechanistic chemotherapeutic drug that has promising anticancer effects with significant potential for further investigation.