DNA-targeting ruthenium(II) complexes that simultaneously induce tumor apoptosis and autophagy

DNA damage is a critical approach in cancer therapy, and the regulation of the cell cycle to inhibit cell proliferation has become an important therapeutic strategy. In this study, two ruthenium(II) complexes, [Ru(phen)₂(1-(p-tolyl)-9H-pyrido[3,4-b]indole)]PF₆ (Ru1) and [Ru(phen)₂(1-(4-chlorophenyl)-9H-pyrido[3,4-b]indole)]PF₆ (Ru2), featuring β-carboline as the primary ligand, were designed and synthesized. The results demonstrated that both Ru1 and Ru2 exhibit significant antitumor activity in vitro. These complexes can bind to DNA in the cell nucleus, induce DNA damage through reactive oxygen species (ROS) generation, and cause S-phase cell cycle arrest. Furthermore, Ru1 effectively triggers autophagy in tumor cells. Ultimately, these mechanisms collectively lead to apoptosis. In summary, we report a DNA-targeting ruthenium complex capable of efficiently inducing DNA damage, promoting autophagy and apoptosis in tumor cells, thereby exerting potent antitumor effects. This work provides a novel strategy for cancer treatment.