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Acta Biochimica et Biophysica Sinica
Year: 2010  |  Volume: 42  |  Issue: 7  |  Page No.: 440 - 449

DNA binding, cytotoxicity, and apoptotic-inducing activity of ruthenium(II) polypyridyl complex

P Zhang, J Chen and Y. Liang    

Abstract:

There is considerable interest in the interactions of ruthenium (Ru)(II) complexes with DNA as well as the biological impact of the interactions. Here, by using isothermal titration calorimetry, viscosity measurement, and circular dichroism, we investigated the interactions of a new Ru(II) complex, [Ru(dmp)2PMIP]2+{dmp = 2,9-dimethyl-1,10-phenanthroline, PMIP = 2-(4-methylphenyl)imidazo[4,5-f]1,10-phenanthroline}, with calf thymus DNA (CT DNA). The Ru(II) polypyridyl complex and CT DNA formed a tight 1:1 complex with a binding constant of exceeding 106 M–1 and with a binding mode of intercalation. Cell viability experiments indicated that the Ru(II) complex showed significant dose-dependent cytotoxicity to human lung tumor cell line A549. Further flow cytometry experiments showed that the cytotoxic Ru(II) complex induced apoptosis of human lung cancer cell line A549. Our data demonstrated that the Ru(II) polypyridyl complex binds to DNA and thereby induces apoptosis in tumor cells, suggesting that anti-tumor activity of the Ru(II) complex could be related to its interaction with DNA.

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