• 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.

• BMB Reports
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• v.29 no.3
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• pp.272-275
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• 1996

The expression of genes induced by Dichloroacetate (DCA) treatment was analyzed by mRNA differential display. Purified total RNAs from rat liver treated with saline or DCA (100 mg/100 g b.w.) were reverse transcribed by using a set of oligonucleotide primers. The PCR products were resolved on a denaturing sequencing gel. PCR band representing mRNA expressed specifically in DCA-treated liver was excised and reamplified by PCR. A 120-bp c-DNA clone named IC1 was isolated and the DNA sequence of IC1 was analyzed. IC1 revealed 50% homology with 3' end of a mouse fibroblast growth factor mRNA This result indicates that DCA induces the expression of a gene which has a 50% homology with a Mouse fibroblast growth factor, and expression of this gene might be involved in non genotoxic process caused by DCA.

• The Korean Journal of Physiology and Pharmacology
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• v.9 no.4
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• pp.195-201
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• 2005

High extracellular glucose concentration was reported to suppress intracellular $Ca^{2+}$ clearing through altered sarcoplasmic reticulum (SR) function. In the present study, we attempted to elucidate the effects of pyruvate and fatty acid on SR function and reveal the mechanistic link with glucose-induced SR dysfunction. For this purpose, SR $Ca^{2+}$-uptake rate was measured in digitonin-permeabilized H9c2 cardiomyocytes cultured in various conditions. Exposure of these cells to 5 mM pyruvate for 2 days induced a significant suppression of SR $Ca^{2+}$-uptake, which was comparable to the effects of high glucose. These effects were accompanied with decreased glucose utilization. However, pyruvate could not further suppress SR $Ca^{2+}$-uptake in cells cultured in high glucose condition. Enhanced entry of pyruvate into mitochondria by dichloroacetate, an activator of pyruvate dehydrogenase complex, also induced suppression of SR $Ca^{2+}$-uptake, indicating that mitochondrial uptake of pyruvate is required in the SR dysfunction induced by pyruvate or glucose. On the other hand, augmentation of fatty acid supply by adding 0.2 to 0.8 mM oleic acid resulted in a dose-dependent suppression of SR $Ca^{2+}$-uptake. However, these effects were attenuated in high glucose-cultured cells, with no significant changes by oleic acid concentrations lower than 0.4 mM. These results demonstrate that (1) increased pyruvate oxidation is the key mechanism in the SR dysfunction observed in high glucose-cultured cardiomyocytes; (2) exogenous fatty acid also suppresses SR $Ca^{2+}$-uptake, presumably through a mechanism shared by glucose.

• Progress in Superconductivity
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• v.9 no.1
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• pp.91-95
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• 2007

[ $YBa_2Cu_3O_{7-{\delta}}$ ] films have been prepared on $LaAlO_3$ (100) single-crystal substrates by the metal organic deposition using dichloroacetate precursors (DCA-MOD). DCA precursor solutions with different composition such as; Yttrium-excess(15 at%), barium-poor(25 at%), and a stoichiometric(Y:Ba:Cu=1:2:3) were prepared in order to investigate the effects of precursor composition on the properties of YBCO films prepared by DCA-MOD method. Coated films were calcined at low temperature up to $500^{\circ}C$ in flowing humid oxygen atmosphere. Conversion heat treatment was performed $800^{\circ}C$ for 2 h in flowing Ar gas containing 1000 ppm oxygen with a humidity of 9.45%. For the film prepared using excess yttrium composition, high critical current density ($J_c$) of $>2MA/cm^2$ was obtained whereas, for the films prepared using barium-poor composition, $J_c$ was lower than $1MA/cm^2$.

• Journal of the Korean Applied Science and Technology
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• v.23 no.2
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• pp.99-109
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• 2006

In order to obtain the maximum flame retardancy as well as the minimum deterioration of physical properties of PU flame-retardant coatings, chlorine and phosphorus functional groups were introduced into the pre-polymer of modified polyesters. In the first step, the tetramethylene bis(orthophosphate) (TBOP) and neohexanediol dichloroacetate (DCA-adduct) intermediates were synthesized. In the second step, 1,4-butanediol and adipic acid monomers were polymerized with the two kinds of intermediates to obtain copolymers. The modified polyesters containing chlorine and phosphorus (ATBA-10C, -20C, and -30C) were synthesized by adjusting that the content of phosphorus compound was fixed as 2wt% and the contents of chlorine compound (dichloroacetic acid) were varied as 10, 20, and 30wt%. Average molecular weight and polydispersity index of the preparation of ATBAs were decreased with increasing DCA content because of the increase in hydroxyl group that retards reaction.

• Progress in Superconductivity
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• v.9 no.1
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• pp.96-101
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• 2007

[ $YBa_2Cu_3O_{7-{\delta}}$ ] films have been prepared on $LaAlO_3$ (100) single-crystal substrates by a metalorganic deposition using dichloroacetate precursors (DCA-MOD). Calcination conditions were varied in order to optimize the microstructure and the superconducting properties of YBCO film. Coated films were calcined at various temperatures ranging from $400{\sim}700^{\circ}C$ in flowing humid oxygen atmosphere. Ramping rate to calcination tempertures was $2.22^{\circ}C/min$. Conversion heat treatment was performed at $800^{\circ}C$ for 2 h in flowing Ar gas containing 1000 ppm oxygen with a humidity of 9.45%. Observations of surface and cross sectional SEM microstructure showed that the particle size in the calcined film increased in the range of 100-200 nm with heating rate and the calcination temperature. SEM EDS analysis showed that 13 a/o of chlorine was contained in the calcined film. It was also observed that the porosity increased with the heating rate and temperature. Porous microstructure was developed when YBCO films were prepared using porous calcined film. Dense microstructure and high $J_c$ over $1\;MA/cm^2$ was obtained when calcination was carried out at the temperature of $500^{\circ}C$ with a heating rate of $2.22^{\circ}C/min$.

• Journal of the Korean Applied Science and Technology
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• v.24 no.2
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• pp.124-139
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• 2007

In order to obtain the maximum flame retardancy with the minimal deterioration of physical properties of PU flame-retardant coatings, chlorine and phosphorous functional groups were introduced into the pre-polymer of modified polyesters. In the first step, the tetramethylene bis(orthophosphate) (TBOP) and neohexanediol dichloroacetate (DCA-adduct) intermediates were synthesized. In the second step, 1,4-butanediol and adipic acid monomers were polymerized with the two kind of intermediates to obtain copolymer. The modified polyesters containing chlorine and phosphorous (ATBA-10C, -20C, and -30C) were synthesized by adjusting the contents of chlorine compound (dichloroacetic acid, 10, 20, 30 wt%) with fixed the content of phosphorous compound (2 wt%). The PU flame-retardant coatings (TTBAH -10C, -20C, and -30C) were prepared using the synthesized ATBAs and HDI-trimer as curing agent at room temperature. The physical properties of PU flame-retardant coatings with chlorine and phosphorous were inferior to those with phosphorous only and the properties were getting worse with increasing chlorine content. Flame retardancy was tested with three methods. With the vertical method, Complete combustion time of ATBAHs were $259^{\sim}347$ seconds, which means that the prepared coatings are good flame-retardant. With the $45^{\circ}$ Meckel burner method, char lengths of the three prepared coatings were less than 2.9 cm, which indicates that the prepared coatings are 1st grade flame retardancy. With the limiting oxygen index (LOI) method, the LOI values of the three prepared coatings were in the range of $30^{\sim}35%$, which proves good flame retardancy of the prepared coatings. From the results of flame retardancy tests of the specimens that contain the same amounts of flame retarding compounds, it was found that the coatings containing both phosphorous and chlorine show higher flame retardancy than the coatings containing phosphorous alone. This indicates that some synergy effect of flame retardancy exists between phosphorous and chlorine.

• Interdisciplinary Bio Central
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• v.1 no.2
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• pp.7.1-7.7
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• 2009

"To be, or not to be?" This question is not only Hamlet's agony but also the dilemma of mitochondria in a cancer cell. Cancer cells have a high glycolysis rate even in the presence of oxygen. This feature of cancer cells is known as the Warburg effect, named for the first scientist to observe it, Otto Warburg, who assumed that because of mitochondrial malfunction, cancer cells had to depend on anaerobic glycolysis to generate ATP. It was demonstrated, however, that cancer cells with intact mitochondria also showed evidence of the Warburg effect. Thus, an alternative explanation was proposed: the Warburg effect helps cancer cells harness additional ATP to meet the high energy demand required for their extraordinary growth while providing a basic building block of metabolites for their proliferation. A third view suggests that the Warburg effect is a defense mechanism, protecting cancer cells from the higher than usual oxidative environment in which they survive. Interestingly, the latter view does not conflict with the high-energy production view, as increased glucose metabolism enables cancer cells to produce larger amounts of both antioxidants to fight oxidative stress and ATP and metabolites for growth. The combination of these two different hypotheses may explain the Warburg effect, but critical questions at the mechanistic level remain to be explored. Cancer shows complex and multi-faceted behaviors. Previously, there has been no overall plan or systematic approach to integrate and interpret the complex signaling in cancer cells. A new paradigm of collaboration and a well-designed systemic approach will supply answers to fill the gaps in current cancer knowledge and will accelerate the discovery of the connections behind the Warburg mystery. An integrated understanding of cancer complexity and tumorigenesis is necessary to expand the frontiers of cancer cell biology.