• Journal of Life Science
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• v.28 no.12
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• pp.1469-1476
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• 2018

Occurrence of the Warburg effect in solid tumors causes resistance to cancer chemotherapy, and targeting energy metabolisms such as aerobic glycolysis is a potential strategy for alternative treatment. Dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinase (PDK), shifts glucose metabolism from aerobic glycolysis to oxidative phosphorylation (OxPhos) in many cancers. In this study, we investigated the anticancer effect of DCA on a human anaplastic thyroid cancer (ATC) cell line, 8505C. We found that DCA selectively inhibits cell proliferation of the 8505C line but not of a normal thyroid line. In 8505C, the cell cycle was arrested at the G1/S phase with DCA treatment as a result of decreased antiapoptotic proteins such as $HIF1{\alpha}$, PDK1, and Bcl-2 and increased proapoptotic proteins such as Bax and p21. DCA treatment enhanced the production of reactive oxygen species which consequently induced cell cycle arrest and apoptosis. Interestingly, DCA treatment not only reduced lactate production but also increased the expression of sodium-iodine symporter, indicating that it restores the OxPhos of glucose metabolism and the iodine metabolism of the ATC. Taken together, our findings suggest that PDK inhibitors such as DCA could be useful anticancer drugs for the treatment of ATC and may also be helpful in combination with chemotherapy and radiotherapy.

• Journal of Nutrition and Health
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• v.4 no.1
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• pp.21-28
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• 1971

1. The effects of chloroform to the tissue lactic dehydrogenase (LDH) activities and its isozymes and to the tissue glutamic dehydrogenase (GDH) activities and its isoaymes are studied using the experimental albino male adult rats in this paper. The tissues studies are liver, kidney, heart, and brain. Besides the control group, two experimental groups are studied providing succeedingly 4 days interpariental administrations of chloroform, 0.0025ml and 0.025ml per day respectively. The changes of body weights, weights of organs, activities of GDH and LDH and their isozymes of each tissues, are analysed. 2. The body weights of rats are decreased due to the chloroform administration. 3. There are no significant differences of weights of organs due to the chloroform administration. 4. The significant decreases of tissue GDH activities and the significant changes in percent distribution of the GDH isozymes are found due to the chloroform administration. This weight be interpretated that chloroform effects to the protein and amino acid metabolism of rats. 5. Due to the chloroform administration, the significant changes in tissue LDH activities and in percent distribution of tissue LDH isozymes indicating the decreases of $LDH_1$ which is the aerobic heart type and the increase of $LDH_5$ which is the anaerobic muscle type, are observed. This could be estimated that chloroform effects to the carbohydrate metabolism, particularly to the anaerobic glycolysis of rats.

• Journal of Korean Traditional Oncology
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• v.20 no.1
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• pp.81-88
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• 2015

Generally, normal cells synthesize adenosine triphosphate (ATP) through oxidative phosphorylation in the mitochondria. However, they produce ATP through lactic acid fermentation on hypoxic condition. Interestingly, many cancer cells rely on aerobic glycolysis for ATP generation instead of mitochondrial oxidative phosphorylation, which is termed as "Warburg effect". According to results from recent researches on differences of cancer cell metabolism from normal cell metabolism and because chemotherapy to suppress rapidly growing cells, as a side effect of cancer treatment, can still target healthy cells, there is merit in the development of small-molecule inhibitors targeting metabolic enzymes such as pyruvate dehydrogenase kinase (PDHK), lactate dehydrogenase (LDH) and monocarboxylate transporter (MCT). For new anticancer therapy, in this review, we show recent advances in study on cancer cell metabolism and molecules targeting metabolic enzymes which are importantly associated with cancer metabolism for cancer therapy. Furthermore, we would also like to emphasize the necessity of development of molecules targeting metabolic enzymes using herbal medicines and their constituents for anticancer drugs.

• BMB Reports
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• v.46 no.2
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• pp.86-91
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• 2013

Glucose effects on the vegetative growth of Dictyostelium discoideum Ax2 were studied by examining oxidative stress and tetrahydropteridine synthesis in cells cultured with different concentrations (0.5X, 7.7 g $L^{-1}$; 1X, 15.4 g $L^{-1}$; 2X, 30.8 g $L^{-1}$) of glucose. The growth rate was optimal in 1X cells (cells grown in 1X glucose) but was impaired drastically in 2X cells, below the level of 0.5X cells. There were glucose-dependent increases in reactive oxygen species (ROS) levels and mitochondrial dysfunction in parallel with the mRNA copy numbers of the enzymes catalyzing tetrahydropteridine synthesis and regeneration. On the other hand, both the specific activities of the enzymes and tetrahydropteridine levels in 2X cells were lower than those in 1X cells, but were higher than those in 0.5X cells. Given the antioxidant function of tetrahydropteridines and both the beneficial and harmful effects of ROS, the results suggest glucose-induced oxidative stress in Dictyostelium, a process that might originate from aerobic glycolysis, as well as a protective role of tetrahydropteridines against this stress.

• The Korean Journal of Zoology
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• v.7 no.2
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• pp.25-36
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• 1964

The present paper deals with the comparative study on phylogenic difference in the patterns of energy metabolism of brain slices of several vertebrate species by measuring oxygen consumptionwith glucose-6-phosphate, glucose-1-phosphate, glyceraldehyde-3-phosphate or glutamate as respiratory substrate employing Warburg's manometric method, by determination of the utilization rate of glucose using glucose-1-C14 by analyzing patterns of free amino acid distribution , and by histochemical determination using glucose-1-C14 by analyzing patterns of free amino acid distribution acid distribution , and by histochemical determination of glycogen contents. 1. Glucose enhances the oxygen consumption of brain slices of animals belinging to reptile, aves and mammalia while it shows a tendency to decrease that of animals belonging to pisces and amphibia. 2. Glucose-6--phosphate increase oxygen consumption more than glucose in every species examined, while glucose-1-phosphate and glyceraldehyde-3-phosphate increase that of Rana nigromaculata only . In general m, it appears that phosphosugars are more effective as a respiratory substrate to those species which have less endogenous respiration than to those having larger endogenous respiration. 3. Similar patterns of free amino acid distribution and the relative amount are found among the species and in every species examined glutamic acid is detected in the larges amount . ${\gamma}$-Amino butyric acid, glycine, alanine and aspartic acid are found in every species. 4. Ophicephalus showed less oxygen consumption than endogenous respiration when glutamate was added to the medium. When sodium fluoride was added, the oxygen consumption was some what increased . Such phenomenon wasnot found in the frog. 5. The result of histochemcial analysis of the brain showed that glycogen was abundantly present in the fish , amphibia , and especially in the reptile and that no distinctive grains of glycogen were found in the bird and mammal . From these facts, it may be supposed that anaerobic glycolysis as energy source dominates in fish and amphibia and aerobic respiration through the oxidation of glucose dominates in bird and mamal , the reptile occupying transitional position between these two categories. The way of obtaining energy for brain activity by the oxidation of glucose supplied from the circulating blood is seemed to be first acquired by reptile and the function is completed both in aves and mammal.

• Journal of Life Science
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• v.31 no.5
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• pp.464-474
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• 2021

Inflammation induced by metabolic syndromes, cancers, injuries, and sepsis can alter cellular metabolism by reducing mitochondrial function via oxidative stress, thereby resulting in neuropathy and muscle atrophy. In this study, we investigated whether butyrate, a short chain fatty acid produced by gut microbiota, could prevent mitochondrial dysfunction and muscle atrophy induced by lipopolysaccharide (LPS) in the C2C12 cell line. LPS-activated MAPK signaling pathways increased the levels of the mitochondrial fission signal, p-DRP1 (Ser616), and the muscle atrophy marker, atrogin 1. Interestingly, butyrate significantly inhibited the phosphorylation of JNK and p38 and reduced the atrogin 1 level in LPS-treated C2C12 cells while increasing the phosphorylation of DRP1 (Ser637) and levels of mitofusin2, which are both mitochondrial fusion markers. Next, we investigated the effect of MAPK inhibitors, finding that butyrate had the same effect as JNK inhibition in C2C12 cells. Also, butyrate inhibited the LPS-induced expression of pyruvate dehydrogenase kinase 4 (PDK4), resulting in decreased PDHE1α phosphorylation and lactate production, suggesting that butyrate shifted glucose metabolism from aerobic glycolysis to oxidative phosphorylation. Finally, we found that these effects of butyrate on LPS-induced mitochondrial dysfunction were caused by its antioxidant effects. Thus, our findings demonstrate that butyrate prevents LPS-induced muscle atrophy by improving mitochondrial dynamics and metabolic stress via the inhibition of JNK phosphorylation. Consequently, butyrate could be used to improve LPS-induced mitochondrial dysfunction and myopathy in sepsis.