title: Cytotoxicity, apoptosis, cellular uptake, cell cycle arrest, photocleavage, and antioxidant activity of 1, 10-phenanthroline ruthenium(II) complexes.
abstract: Two new ruthenium(II) complexes, [Ru(phen)2(DNPIP)](ClO4)2 (1) and [Ru(phen)2(DAPIP)](ClO4)2 (2), were synthesized and characterized. The DNA-binding properties of these complexes were investigated using UV/vis absorption titration, viscosity measurements, thermal denaturation, and photoactivated cleavage. The DNA binding constants for complexes 1 and 2 are 2.63 ± 0.25×10(5) M(-1) (s=2.45) and 1.51±0.18×10(5) M(-1) (s=1.34). The results indicated that these complexes interacted with DNA through the intercalative mode. The cytotoxicity in vitro of complexes 1 and 2 were assessed against BEL-7402, HepG-2, and MCF-7 cell lines by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was studied with the acridine orange/ethidium bromide staining method. The antiproliferative mechanism was explored with flow cytometry. Cellular uptake studies showed that complexes 1 and 2 can enter into the cytoplasm and accumulate in the nuclei. Cell cycle arrest and antioxidant activity were also investigated.
authors.affiliation: School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, PR China. lyjche@163.com
authors.forename: Yun-Jun
authors.initials: YJ
authors.lastname: Liu
authors.forename: Zheng-Zheng
authors.initials: ZZ
authors.lastname: Li
authors.forename: Zhen-Hua
authors.initials: ZH
authors.lastname: Liang
authors.forename: Jun-Hua
authors.initials: JH
authors.lastname: Yao
authors.forename: Hong-Liang
authors.initials: HL
authors.lastname: Huang
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D000975:Antioxidants / Q000138:chemical synthesis / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D005434:Flow Cytometry; D005453:Fluorescence; D006801:Humans; D017665:Hydroxyl Radical / Q000037:antagonists & inhibitors / Q000378:metabolism; D007364:Intercalating Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D007700:Kinetics; D008113:Liver Neoplasms / Q000188:drug therapy / Q000473:pathology; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000494:pharmacology*; D010084:Oxidation-Reduction / Q000187:drug effects / Q000528:radiation effects; D010618:Phenanthrolines / Q000737:chemistry; D010782:Photolysis / Q000528:radiation effects; D010957:Plasmids / Q000378:metabolism; D012428:Ruthenium / Q000737:chemistry / Q000378:metabolism*; D013057:Spectrum Analysis; D014466:Ultraviolet Rays
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D007364:Intercalating Agents; D009942:Organometallic Compounds; D010618:Phenanthrolines; D017665:Hydroxyl Radical; D012428:Ruthenium; D004247:DNA; C427203:calf thymus DNA