The mesoionic compound MI-D changes energy metabolism and induces apoptosis in T98G glioma cells

Regulative Roles of Metabolic Plasticity Caused by Mitochondrial Oxidative Phosphorylation and Glycolysis on the Initiation and Progression of Tumorigenesis

“…The insufficient energy supply caused by the inhibition of glycolysis due to the excessive increase in citric acid can be attributed to mitochondrial oxidative metabolism. In mitochondria, citric acid is a key regulator of mitochondrial oxidation enzymes, such as successful dehydrogenase (SDH), PDH, and Carnitine Palmitoyl Transfer I (CPT) [ 203 , 204 , 205 , 206 , 207 ]. However, as previously mentioned, the increase in the TCA cycle and the enhancement of OXPHOS caused by metabolic remodeling may also be features of mitochondrial dysfunction in tumour cells, and citric acid plays an important role in this process [ 151 , 152 , 153 ].…”

“…For example, when T98G glioma cells were cultured in a medium containing galactose and an increased concentration of glucose (DMEM GAL medium), the citrate synthase activity was increased by 26%, and the corresponding citric acid was also increased. Correspondingly, TCA increased, and the level of glycolysis was weakened, reflecting the metabolic remodeling process from glycolysis to OXPHOS [ 205 ]. The authors believe mitochondria may become more sensitive to some mitochondria-targeted drugs under this condition.…”

“…Therefore, the MI–D compound [4-phenyl-5-(4-nitro-cinnamoyl)-1,3,4-thiadiazolium-2-phenylamine], a potential candidate mitochondria-targeting drug [ 219 ], was used. They found that the MI–D compound can effectively enhance the activity of citrate synthase and citric acid and induce tumour metabolic remodelling, and, correspondingly, the tumour-killing effect of the drug is more obvious [ 205 ]. The above results explain the mechanism by which MI-D, an anticancer drug, can produce a more effective tumour-killing effect under the condition of inducing tumour metabolic remodelling.…”