title: A ruthenium(II) β-carboline complex induced p53-mediated apoptosis in cancer cells.
abstract: A ruthenium(II) β-carboline complex [Ru(tpy)(Nh)3](2+) (tpy = 2,2':6',2″-terpyridine, Nh = Norharman, Ru1) has been synthesized and characterized. This complex induced apoptosis against various cancer cell lines and had high selectivity between tumor cells and normal cells. In vivo examination indicated Ru1 decreased mouse MCF-7 and HepG2 tumor growth. Signaling pathways analysis demonstrated that this complex induced apoptosis via the mitochondrial pathway, as evidenced by the loss of mitochondrial membrane potential (MMP, ΔΨm) and the release of cytochrome c. The resulting accumulation of p53 proteins from phosphorylation at Ser-15 and Ser-392 correlated with an increase in p21 and caspase activation. Taken together, these findings suggest that Ru1 exhibits high and selective cytotoxicity induced p53-mediated apoptosis and 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: 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: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002243:Carbolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D061986:MCF-7 Cells; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D012428:Ruthenium / Q000737:chemistry / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D002243:Carbolines; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D012428:Ruthenium; D045304:Cytochromes c
keywords: Anticancer; Apoptosis; Ruthenium(II) complex; p53; β-Carboline