• Title/Summary/Keyword: dichloroacetate (DCA) treatment

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Dichloroacetate Inhibits the Proliferation of a Human Anaplastic Thyroid Cancer Cell Line via a p53-independent Pathway (Dichloroacetate의 p53 비의존적 경로를 통한 인간 역분화 갑상선 암세포주의 성장억제 효과)

  • KC, Yam Bahadur;Poudel, Sunil;Jeon, Eon Ju;Shon, Ho Sang;Byun, Sung June;Jeoung, Nam Ho
    • 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.

Differential Display Analysis of Gene Expression Induced under DCA Treatment in Rat Liver

  • Choi, Soon-Yong;Park, Ock-Jin
    • 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.

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Effects of Precursor Composition on the $J_c$ of YBCO thin Films Prepared by DCA-MOD Method (DCA-MOD 방법으로 제조하는 YBCO 박막의 임계전류밀도에 미치는 전구체 조성의 효과)

  • Kim, Byeone-Jin;Kim, Hye-Joo;Lee, Jong-Beum;Lee, Hee-Gyoun;Hong, Gye-Won
    • 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 $1MA/cm^2$.

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Effects of Heat Treatments on the Microstructure of YBCO Films Prepared by DCA-MOD Method (DCA-MOD 방법으로 제조된 YBCO 박막의 미세조직에 미치는 열처리 효과)

  • Kim, Byeong-Joo;Kim, Hye-Jin;Cho, Han-Woo;Yu, Seok-Koo;Ryu, Jung-Hee;Lee, Hee-Gyoun;Hong, Gye-Won
    • 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 $2.22^{\circ}C/min$.

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