title: Apoptotic mechanisms of N1-acetylacetone, N4-4-methoxy-salicylidene-thiosemicarbazide chelating with Nickel(II) on HL60 leukemia cells.
abstract: Thiosemicarbozone complexes that have a broad spectrum of biological activity are formed as a result of condensation reaction between thiosemicarbazide [H2N(C=S)-NH-NH2] and carbonyl-containing compounds. A new Nickel(II) complexes with N1-acetylacetone, N4-4-methoxy-salicylidene-thiosemicarbazidato ligand was synthesized and characterized. We studied the antileukemic activity of the Ni(II) thiosemicarbazone compound and assessed their potential for drug development. Specifically, the effects of this Ni(II) thiosemicarbazone compound on intracellular signal nodes and apoptotic pathways were investigated. According to our results, the Ni(II) thiosemicarbazone compound has apoptotic activity against HL60 cells. Moreover, while Ni(II) thiosemicarbazone compound significantly increased levels of p53 and cleaved caspase-3 proteins, it decreased level of Phospho-Akt1 protein in HL60 cells. The Ni(II) thiosemicarbazone compound could induce HL60 cell apoptosis through inhibiting of PI3K/Akt pathway. These results showed that Ni(II) thiosemicarbozone compound might be an antileukemic agent.
authors.affiliation: Department of Chemistry, Faculty of Engineering, İstanbul University, Istanbul, Turkey.
authors.forename: Büşra
authors.initials: B
authors.lastname: Kaya
authors.forename: Belkis
authors.initials: B
authors.lastname: Atasever-Arslan
authors.forename: Zeynep
authors.initials: Z
authors.lastname: Kalkan
authors.forename: Hazal
authors.initials: H
authors.lastname: Gür
authors.forename: Bahri
authors.initials: B
authors.lastname: Ülküseven
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000138:chemical synthesis; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D002614:Chelating Agents / Q000032:analysis / Q000737:chemistry; D018922:HL-60 Cells; D006801:Humans; D009532:Nickel / Q000008:administration & dosage* / Q000737:chemistry; D012663:Semicarbazides / Q000008:administration & dosage* / Q000138:chemical synthesis; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D002614:Chelating Agents; D012663:Semicarbazides; C005151:thiosemicarbazide; D009532:Nickel