Ruthenium(II) coordinated with diphenylphosphine and 2-mercaptothiazoline as a selective antiproliferative agent in breast cancer cells

Abstract Breast cancer is the most common malignant neoplasm among women and exhibits high molecular heterogeneity, which directly influences therapeutic response and clinical outcomes. Despite advances in targeted therapies and immunotherapies, tumor recurrence, resistance to conventional treatments, and metastatic potential reinforce the need for more selective and effective pharmacological strategies. In this context, metal complexes, particularly ruthenium(II) derivatives, have attracted considerable attention due to their antitumor profile, greater selectivity, and lower systemic toxicity. Therefore, in the present study, the antineoplastic activity of the RuMTZ complex (2-mercaptothiazoline-di-1,2-bis(diphenylphosphine)ethane-ruthenium(II)) was evaluated in three breast cancer cell lines (MDA-MB-231, MDA-MB-468 and MCF7) and in one non-tumor breast cell line (MCF10A). RuMTZ exhibited greater cytotoxicity against human MDA-MB-468 cells, as demonstrated by cell viability (IC 50 = 1.8 µM) and clonogenic (IC 50 = 0.08 µM) assays, associated with higher selectivity indexes (3.89 and 3.75, respectively). Further studies demonstrated that RuMTZ inhibited cell migration by up to 62.76% and induced cell-cycle arrest in the G0/G1 phase, accompanied by a reduction in the G2/M population. Furthermore, the ruthenium complex induced apoptotic cell death, as observed by flow cytometry and increased levels of cleaved caspase-3 by Western blot. The genotoxic effect of RuMTZ was evidenced by the comet assay and increased γH2AX expression levels. Taken together, these findings demonstrate that RuMTZ exhibits promising antineoplastic activity against breast cancer cells, associated with cell-cycle arrest, induction of DNA damage, and apoptosis.