Synthesis, characterization, and anticancer activity of ruthenium(II)-β-carboline complex

Four [Ru(tpy)(N-N)(L)] type complexes: [Ru(tpy)(bpy)(Nh)](2+) (Ru1, tpy = 2,2';6',2″-terpyridine, bpy = 2'2-bipyridine, Nh = Norharman), [Ru(tpy)(phen)(Nh)](2+) (Ru2, phen = 1,10-phenanthroline), [Ru(tpy)(dpa)(Nh)](2+) (Ru3, dpa = 2,2'-dipyridylamine) and [Ru(tpy)(dip)(Nh)](2+) (Ru4, dip = 4,7-diphenyl-1,10-phenanthroline) were presented as anticancer drugs. In vitro cytotoxicity assays indicated that these complexes showed anticancer activity against various cancer cells. Flow cytometry and signaling pathways analysis demonstrated that these complexes induced apoptosis via the mitochondrial pathway, as evidenced by the loss of mitochondrial membrane potential and the release of cytochrome c. The resulting accumulation of p53 proteins from phosphorylation at serine-15 and serine-392 was correlated with an increase in p21 and caspase activation. Taken together, these findings suggested that Ru1-Ru4 may contribute to the future development of improved chemotherapeutics against human cancers.