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

The use of benzimidazole-based
trinuclear ruthenium(II)–arene
complexes (1–3) 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 1 was noted to show
superior short- and long-term cytotoxicity in RMS cell lines and enhanced
selectivity relative to cisplatin. Remarkably, 1 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 1 effectively induces genomic DNA damage, initiates autophagy,
and prompts the intrinsic and extrinsic apoptotic pathways in RMS
cells. To the best of our knowledge, 1 is the first trinuclear
ruthenium(II) arene complex to selectively kill RMS cells in 2D and
3D cell cultures.