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KMID : 0613820180280121469
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Journal of Life Science
2018 Volume.28 No. 12 p.1469 ~ p.1476
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Dichloroacetate Inhibits the Proliferation of a Human Anaplastic Thyroid Cancer Cell Line via a p53-independent Pathway
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Yam Bahadur KC
Poudel Sunil
Jeon Eon-Ju
Shon Ho-Sang
Byun Sung-June
Jeoung Nam-Ho
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Abstract
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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 HIF1α, 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.
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KEYWORD
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Anaplastic thyroid cancer, apoptosis, cell cycle arrest, dichloroacetate, Warburg effect
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