DNA binding, cytotoxicity, and apoptotic-inducing activity of ruthenium(II) polypyridyl complex.
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)(2)PMIP](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 10(6) 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.
Zhang
Peng
P
Wuhan University, China.
Chen
Jie
J
Liang
Yi
Y
D015082:2,2'-Dipyridyl / Q000737:chemistry; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001667:Binding, Competitive; D002151:Calorimetry; D002417:Cattle; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D007364:Intercalating Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D015394:Molecular Structure; D009690:Nucleic Acid Conformation; D009942:Organometallic Compounds / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D012428:Ruthenium / Q000737:chemistry*; D013816:Thermodynamics
D007364:Intercalating Agents; D009942:Organometallic Compounds; D015082:2,2'-Dipyridyl; D012428:Ruthenium; D004247:DNA; C427203:calf thymus DNA