Chiral ruthenium(II) complex as potent radiosensitizer of 125I through DNA-damage-mediated apoptosis

A chiral ruthenium(II) complex, Λ-[Ru(bpy)2(o-tFMPIP)] (ClO4)2 (o-tFMPIP = 2′-trifluoromethylphenyl) imidazo [4,5-f][1,10]phenanthroline, was prepared and evaluated for its enhancement of the radiosensitivity of 125I seeds. The synthetic Ru(II) complex, LR042, effectively enhanced growth inhibition against HepG2 human hepatocellular liver carcinoma cells induced by 125I seeds and consequently effectively promoted the apoptosis of tumor cells with increasing level of cleave-caspase-3. Furthermore, the results of immunofluorescence indicated that LR042 enhanced the phosphorylation of H2AX by 125I seeds vigorously in response to damaged DNA. LR042 improved DNA damage induced by 125I seeds, which resulted in apoptosis through the activation of the p53/AKT signal. In conclusion, synthetic LR042 can be further developed as a potential radiosensitizer of 125I seed radiotherapy for cancer therapy.