Selective Targeting of Regulated Rhabdomyosarcoma Cells by Trinuclear Ruthenium(II)-Arene Complexes.

The use of benzimidazole-based trinuclear ruthenium(II)-arene complexes (-) to selectively target the rare cancer rhabdomyosarcoma is reported. Preliminary cytotoxic evaluations of the ruthenium complexes in an eight-cancer cell line panel revealed enhanced, selective cytotoxicity toward rhabdomyosarcoma cells (RMS). The trinuclear complex was noted to show superior short- and long-term cytotoxicity in RMS cell lines and enhanced selectivity relative to cisplatin. Remarkably, inhibits the migration of metastatic RMS cells and maintains superior activity in a 3D multicellular spheroid model in comparison to that of the clinically used cisplatin. Mechanistic insights reveal that effectively induces genomic DNA damage, initiates autophagy, and prompts the intrinsic and extrinsic apoptotic pathways in RMS cells. To the best of our knowledge, is the first trinuclear ruthenium(II) arene complex to selectively kill RMS cells in 2D and 3D cell cultures.