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- Title
The mesoionic compound MI-D changes energy metabolism and induces apoptosis in T98G glioma cells.
- Authors
Corrêa-Ferreira, Marília Locatelli; do Rocio Andrade Pires, Amanda; Barbosa, Igor Resendes; Echevarria, Aurea; Pedrassoli, Guilherme Henrique; Winnischofer, Sheila Maria Brochado; Noleto, Guilhermina Rodrigues; Cadena, Sílvia Maria Suter Correia
- Abstract
The mesoionic compound 4-phenyl-5-(4-nitro-cinnamoyl)-1,3,4-thiadiazolium-2-phenylamine chloride (MI-D) impairs mitochondrial oxidative phosphorylation and has a significant antitumour effect against hepatocarcinoma and melanoma. This study evaluated the cytotoxic effect of MI-D on T98G glioblastoma cells and investigated whether the impairment of oxidative phosphorylation promoted by MI-D is relevant to its cytotoxic effect. The effects of MI-D on T98G cells cultured in high glucose Dulbecco's modified Eagle's medium (DMEM) HG (glycolysis-dependent) and galactose plus glutamine-supplemented Dulbecco's modified Eagle's medium (DMEM) GAL (oxidative phosphorylation-dependent) were compared. T98G cells grown in DMEM GAL medium exhibited higher respiration rates and citrate synthase activity and lower lactate levels, confirming the metabolic shift to oxidative phosphorylation in these cells. MI-D significantly decreased the cell viability in a dose-dependent manner in both media; however, T98G cells cultured in DMEM GAL medium were more susceptible. The mesoionic significantly inhibited mitochondrial oxidative phosphorylation of glioma cells in both media. At the same time, lactate levels were not altered, indicating an absence of compensatory glycolysis activation. Additionally, MI-D increased the citrate synthase activity of cells in both media, which in DMEM HG-cultivated cells was followed by citrate accumulation. Apoptosis dependent on caspase-3 mediated the toxicity of MI-D on T98G cells. The higher susceptibility of glioma cells cultured in DMEM GAL medium to MI-D indicates that the impairment of mitochondrial functions is involved in mesoionic cytotoxicity. The results of this study indicate the potential use of MI-D for glioblastoma treatment.
- Subjects
MESOIONIC compounds; ENERGY metabolism; GLIOMAS; CITRATE synthase; OXIDATIVE phosphorylation; APOPTOSIS; GLYCOLYSIS; RESPIRATION
- Publication
Molecular & Cellular Biochemistry, 2022, Vol 477, Issue 8, p2033
- ISSN
0300-8177
- Publication type
Article
- DOI
10.1007/s11010-022-04423-2