title: Synthesis, characterization, and anticancer activity of ruthenium(II)-β-carboline complex.
abstract: Four [Ru(tpy)(N-N)(L)] type complexes: [Ru(tpy)(bpy)(Nh)](2+) (Ru1, tpy = 2,2';6',2″-terpyridine, bpy = 2'2-bipyridine, Nh = Norharman), [Ru(tpy)(phen)(Nh)](2+) (Ru2, phen = 1,10-phenanthroline), [Ru(tpy)(dpa)(Nh)](2+) (Ru3, dpa = 2,2'-dipyridylamine) and [Ru(tpy)(dip)(Nh)](2+) (Ru4, dip = 4,7-diphenyl-1,10-phenanthroline) were presented as anticancer drugs. In vitro cytotoxicity assays indicated that these complexes showed anticancer activity against various cancer cells. Flow cytometry and signaling pathways analysis demonstrated that these complexes induced apoptosis via the mitochondrial pathway, as evidenced by the loss of mitochondrial membrane potential and the release of cytochrome c. The resulting accumulation of p53 proteins from phosphorylation at serine-15 and serine-392 was correlated with an increase in p21 and caspase activation. Taken together, these findings suggested that Ru1-Ru4 may contribute to the future development of improved chemotherapeutics against human cancers.
authors.affiliation: State Key Laboratory of Biocontrol, Department of Biochemistry, College of Life Sciences, Sun Yat-sen University, Guangzhou 510006, PR China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.forename: Meng-Ying
authors.initials: MY
authors.lastname: Qin
authors.forename: Jing-Heng
authors.initials: JH
authors.lastname: Wu
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Hui
authors.initials: H
authors.lastname: Chao
authors.forename: Liang-Nian
authors.initials: LN
authors.lastname: Ji
authors.forename: An-Long
authors.initials: AL
authors.lastname: Xu
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002243:Carbolines / Q000737:chemistry*; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D045325:HCT116 Cells; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D061986:MCF-7 Cells; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012428:Ruthenium / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D002243:Carbolines; D009942:Organometallic Compounds; D017382:Reactive Oxygen Species; D012428:Ruthenium
keywords: 1,10-phenanthroline; 2,2′-bipyridine; 2,2′-dipyridylamine; 2,2′:6′,2″-terpyridine; 2′,7′-dichlorofluorescein-diacetate; 4,5-dihydroxy-1,3-benzenedisulfonic acid disodium salt; 4,7-dibenzyl-1,10-phenanthroline; Apoptosis; CCCP; DCFH-DA; Mitochondria; N-acetylcysteine; NAC; Nh; Norharman; PI; Ruthenium(II) complex; bpy; carbonyl cyanide m-chlorophenylhydrazone; dip; dpa; p53; phen; propidium iodide; tiron; tpy; β-Carboline