title: Cytotoxicity, apoptosis, cellular uptake, cell cycle distribution, and DNA-binding investigation of ruthenium complexes.
abstract: Three new ruthenium(II) polypyridyl complexes [Ru(bpy)(2)(BHIP)](2+) 1, [Ru(phen)(2)(BHIP)](2+) 2, and [Ru(dip)(2)(BHIP)](2+) 3 were synthesized and characterized. The cytotoxicity of the three complexes was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The apoptosis induced by the complexes was studied by cell morphology and flow cytometry. The results showed that the percentage of apoptotic cells is 7.19%, 75.58%, and 3.51% in the presence of complexes 1, 2, and 3, respectively. The cellular uptakes were also performed and the results indicated that complexes 1, 2, and 3 can enter into the cytoplasm and also into the nucleus. The studies on antiproliferative mechanism showed the induction of S-phase arrest by complexes 1, 2, and 3. DNA-binding constants of these complexes with calf thymus DNA (CT-DNA) were determined to be 1.07 (± 0.47) × 10(5) M(-1) (s = 2.04), 1.21 (± 0.32) × 10(5) M(-1) (s = 1.88), and 2.75 (± 0.27) × 10(5) M(-1) (s = 2.17), respectively. Upon irradiation at 365 nm, complexes 1, 2, and 3 can induce cleavage of pBR322 DNA.
authors.affiliation: Department of Orthopaedics, Guangzhou First Municipal People's Hospital, Affiliated to Guangzhou Medical College, Guangzhou, PR China. qifengguo@163.com
authors.forename: Qi-Feng
authors.initials: QF
authors.lastname: Guo
authors.forename: Si-Hong
authors.initials: SH
authors.lastname: Liu
authors.forename: Qing-Hua
authors.initials: QH
authors.lastname: Liu
authors.forename: Hui-Hua
authors.initials: HH
authors.lastname: Xu
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Zhao
authors.forename: Hai-Feng
authors.initials: HF
authors.lastname: Wu
authors.forename: Xin-Yan
authors.initials: XY
authors.lastname: Li
authors.forename: Jian-Wei
authors.initials: JW
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001692:Biological Transport; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D045744:Cell Line, Tumor; D004247:DNA / Q000378:metabolism*; D006801:Humans; D009942:Organometallic Compounds / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D055668:Photochemical Processes; D012428:Ruthenium / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D012428:Ruthenium; D004247:DNA