title: Autophagy and apoptosis: studies on the effects of bisthiosemicarbazone copper(ii) complexes on p53 and p53-null tumour cell lines.
abstract: A comparative study between two bisthiosemicarbazones, 2,3-butanedione bis(4,4-dimethyl-3-thiosemicarbazone) and 2,3-butanedione bis(2-methyl-3-thiosemicarbazone), and their copper(ii) complexes is reported. The four compounds have been tested on a leukemia cell line U937 (p53-null) and on an adenocarcinoma cell line A549. The study includes cell viability, cell cycle, morphological changes, assessment of apoptosis, analysis of autophagy, measurement of reactive oxygen species (ROS) and of lipid peroxidation, protein determination, assessment of the expression of p53 and cellular uptake of metal complexes. Tests about the copper uptake under normoxic and hypoxic conditions were also carried out on a solid tumour cell line A549. The four compounds under study elicit different effects on the two lines adopted as representatives of p53 and p53-null cells. The role of the metal is relevant and it is likely that the metal-mediated oxidative stress plays an essential role in the whole process. The mechanisms induced by these molecules differ not only as a function of the cell line but also of dose. The responses include two distinct self-destructive processes, autophagy and apoptosis.
authors.affiliation: Department of Chemistry, University of Parma, Parma, Italy. giorgio.pelosi@unipr.it and Inter-University Consortium for Research on Chemistry of Metals in Biological Systems (C.I.R.C.M.S.B.), Parma Research Unit, 43124 Parma, Italy.
authors.forename: Franco
authors.identifier: 0000-0001-9165-0356
authors.initials: F
authors.lastname: Bisceglie
authors.affiliation: Inter-University Consortium for Research on Chemistry of Metals in Biological Systems (C.I.R.C.M.S.B.), Parma Research Unit, 43124 Parma, Italy and Laboratory of Industrial Toxicology, Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy.
authors.forename: Rossella
authors.initials: R
authors.lastname: Alinovi
authors.affiliation: Inter-University Consortium for Research on Chemistry of Metals in Biological Systems (C.I.R.C.M.S.B.), Parma Research Unit, 43124 Parma, Italy and Laboratory of Industrial Toxicology, Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy.
authors.forename: Silvana
authors.initials: S
authors.lastname: Pinelli
authors.affiliation: Laboratory of Industrial Toxicology, Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy.
authors.forename: Maricla
authors.initials: M
authors.lastname: Galetti
authors.affiliation: Department of Chemistry, University of Parma, Parma, Italy. giorgio.pelosi@unipr.it.
authors.forename: Marianna
authors.identifier: 0000-0003-3352-7872
authors.initials: M
authors.lastname: Pioli
authors.affiliation: Department of Chemistry, University of Parma, Parma, Italy. giorgio.pelosi@unipr.it and Inter-University Consortium for Research on Chemistry of Metals in Biological Systems (C.I.R.C.M.S.B.), Parma Research Unit, 43124 Parma, Italy.
authors.forename: Pieralberto
authors.initials: P
authors.lastname: Tarasconi
authors.affiliation: Laboratory of Industrial Toxicology, Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Mutti
authors.affiliation: Laboratory of Industrial Toxicology, Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Goldoni
authors.affiliation: Department of Chemistry, University of Parma, Parma, Italy. giorgio.pelosi@unipr.it and Inter-University Consortium for Research on Chemistry of Metals in Biological Systems (C.I.R.C.M.S.B.), Parma Research Unit, 43124 Parma, Italy.
authors.forename: Giorgio
authors.identifier: 0000-0002-7946-0602
authors.initials: G
authors.lastname: Pelosi
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D003300:Copper / Q000737:chemistry; D016158:Genes, p53; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects; D013057:Spectrum Analysis; D013882:Thiosemicarbazones / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D013882:Thiosemicarbazones; D003300:Copper