Antitumor Effect of Ruthenium(II) with 2-Mercaptothiazoline Ligand Complex in Murine Melanoma Model

Abstract

Ruthenium-based complexes have been explored as promising alternatives in antineoplastic therapy due to their enhanced selectivity for cancer cells. In this context, the present study evaluated the antitumor potential of the ruthenium complex [Ru(mtz)(dppe)2]PF6, named RuMTZ, in C57BL/6 mice bearing B16-melanoma, as well as its toxicity. In addition to tumor weight and mitotic frequency, cleaved caspase-3, γH2AX, and MAPK/ERK expression levels were analyzed by immunohistochemistry. The toxicity of the treatments was assessed through alterations in body and organ weight, biochemical parameters of liver and kidney function, and genotoxicity in bone marrow cells. RuMTZ led to a significant reduction in mitotic frequency and tumor weight, with a tumor growth inhibition rate equivalent to 94.9%. The antimelanoma activity of RuMTZ was accompanied by increased levels of cleaved caspase-3, γH2AX, and MAPK/ERK. These data indicate that RuMTZ induced DNA strand breaks, which may be, at least in part, related to the induction of caspase- and ERK1/2-mediated apoptosis. RuMTZ treatment, unlike cisplatin, showed no weight loss or impairment of liver and kidney functions. However, similar to other metallopharmaceuticals, it caused myelosuppression, evidenced by the absence of erythrocytes. These findings support the promising antitumor activity of RuMTZ, indicating its potential as a metallodrug.