Impairment of oxidative phosphorylation increases the toxicity of SYD-1 on hepatocarcinoma cells (HepG2).

Autor: Brandt AP; Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Paraná, Curitiba, Paraná, Brazil., Gozzi GJ; Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Paraná, Curitiba, Paraná, Brazil., Pires Ado R; Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Paraná, Curitiba, Paraná, Brazil., Martinez GR; Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Paraná, Curitiba, Paraná, Brazil., Dos Santos Canuto AV; Departamento de Química, Universidade Federal Rural do Rio de Janeiro, Rio de Janeiro, Brazil., Echevarria A; Departamento de Química, Universidade Federal Rural do Rio de Janeiro, Rio de Janeiro, Brazil., Di Pietro A; MMSB UMR 5086 CNRS/Université Lyon 1, IBCP, Lyon, France., Cadena SM; Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Paraná, Curitiba, Paraná, Brazil. Electronic address: silvia.cadena@ufpr.br.
Jazyk: angličtina
Zdroj: Chemico-biological interactions [Chem Biol Interact] 2016 Aug 25; Vol. 256, pp. 154-60. Date of Electronic Publication: 2016 Jul 11.
DOI: 10.1016/j.cbi.2016.07.007
Abstrakt: 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.
(Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)
Databáze: MEDLINE
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