title: Impairment of oxidative phosphorylation increases the toxicity of SYD-1 on hepatocarcinoma cells (HepG2).
abstract: Toxicity of the SYD-1 mesoionic compound (3-[4-chloro-3-nitrophenyl]-1,2,3-oxadiazolium-5-olate) was evaluated on human liver cancer cells (HepG2) grown in either high glucose (HG) or galactose (GAL) medium, and also on suspended cells kept in HG medium. SYD-1 was able to decrease the viability of cultured HepG2 cells in a dose-dependent manner, as assessed by MTT, LDH release and dye with crystal violet assays, but no effect was observed on suspended cells after 1-40 min of treatment. Respiration analysis was performed after 2 min (suspended cells) or 24 h (cultured cells) of treatment: no change was observed in suspended cells, whereas SYD-1 inhibited as well basal, leak and uncoupled states of the respiration in cultured cells with HG medium. These inhibitions were consistent with the decrease in pyruvate level and increase in lactate level. Even more extended results were obtained with HepG2 cells grown in GAL medium where, additionally, the ATP amount was reduced. Furthermore, SYD-1 appears not to be transported by the main ABC multidrug transporters. These results show that SYD-1 is able to change the metabolism of HepG2 cells, and suggest that its cytotoxicity is related to impairment of mitochondrial metabolism. Therefore, we may propose that SYD-1 is a potential candidate for hepatocarcinoma treatment.
authors.affiliation: Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Paraná, Curitiba, Paraná, Brazil.
authors.forename: Anna Paula
authors.initials: AP
authors.lastname: Brandt
authors.affiliation: Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Paraná, Curitiba, Paraná, Brazil.
authors.forename: Gustavo Jabor
authors.initials: GJ
authors.lastname: Gozzi
authors.affiliation: Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Paraná, Curitiba, Paraná, Brazil.
authors.forename: Amanda do Rocio Andrade
authors.initials: Ado R
authors.lastname: Pires
authors.affiliation: Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Paraná, Curitiba, Paraná, Brazil.
authors.forename: Glaucia Regina
authors.initials: GR
authors.lastname: Martinez
authors.affiliation: Departamento de Química, Universidade Federal Rural do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: André Vinícius
authors.initials: AV
authors.lastname: Dos Santos Canuto
authors.affiliation: Departamento de Química, Universidade Federal Rural do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Aurea
authors.initials: A
authors.lastname: Echevarria
authors.affiliation: MMSB UMR 5086 CNRS/Université Lyon 1, IBCP, Lyon, France.
authors.forename: Attilio
authors.initials: A
authors.lastname: Di Pietro
authors.affiliation: Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Paraná, Curitiba, Paraná, Brazil. Electronic address: silvia.cadena@ufpr.br.
authors.forename: Sílvia Maria Suter Correia
authors.initials: SM
authors.lastname: Cadena
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D010069:Oxadiazoles / Q000494:pharmacology*; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D019289:Pyruvic Acid / Q000378:metabolism
chemical_list: C524256:3-(4-chloro-3-nitrolphenyl)-1,2,3-oxadiazolium-5-olate; D000970:Antineoplastic Agents; D010069:Oxadiazoles; D019344:Lactic Acid; D019289:Pyruvic Acid; D000255:Adenosine Triphosphate
keywords: Hepatocarcinoma; Mesoionics; Mitochondrial bioenergetics; SYD-1