Open Access

Dichloroacetate induces protective autophagy in esophageal squamous carcinoma cells

  • Authors:
    • Hong‑Yu Jia
    • He‑Nan Wang
    • Feng‑Yu Xia
    • Yan Sun
    • Hong‑Li Liu
    • Li‑Li Yan
    • Shan‑Shan Li
    • Dong‑Chun Jiang
    • Mei‑Mei Xu
  • View Affiliations

  • Published online on: July 8, 2017     https://doi.org/10.3892/ol.2017.6562
  • Pages: 2765-2770
  • Copyright: © Jia et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Dichloroacetate (DCA) is an inhibitor of pyruvate dehydrogenase kinase, which promotes the flux of carbohydrates into mitochondria and enhances the aerobic oxidation of glucose. DCA has previously been demonstrated to exhibit antitumor properties. The present study revealed that treatment with DCA induced increased levels of autophagy‑associated proteins in esophageal squamous carcinoma cells while minimally affecting apoptosis. The present study examined the localization of light chain (LC)‑3 by adenovirus infection with a green fluorescent protein (FP)‑red FP‑LC3 reporter construction and confirmed that DCA treatment induced significant autophagy. Furthermore, the inhibition of DCA‑induced autophagy facilitated cell apoptosis and improved the drug sensitivity of esophageal squamous carcinoma cells to DCA and 5‑FU (5‑fluorouracil). The proliferation of TE‑1 cells was markedly inhibited at low concentrations of DCA and 5‑FU treatment when subjected to Atg5 mRNA interference, indicating that autophagy performed a protective role in cell survival upon DCA treatment. To determine the underlying mechanism of DCA‑induced autophagy, the present study measured alterations in autophagy‑associated signaling pathways. Notably, the protein kinase B (Akt)‑mechanistic target of rapamycin (mTOR) signaling pathway, an important negative regulator of autophagy, was demonstrated to be suppressed by DCA treatment. These results may direct the development of novel strategies for the treatment of esophageal squamous carcinoma based on the combined use of DCA and autophagy inhibitors.
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September-2017
Volume 14 Issue 3

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Copy and paste a formatted citation
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Spandidos Publications style
Jia HY, Wang HN, Xia FY, Sun Y, Liu HL, Yan LL, Li SS, Jiang DC and Xu MM: Dichloroacetate induces protective autophagy in esophageal squamous carcinoma cells. Oncol Lett 14: 2765-2770, 2017.
APA
Jia, H., Wang, H., Xia, F., Sun, Y., Liu, H., Yan, L. ... Xu, M. (2017). Dichloroacetate induces protective autophagy in esophageal squamous carcinoma cells. Oncology Letters, 14, 2765-2770. https://doi.org/10.3892/ol.2017.6562
MLA
Jia, H., Wang, H., Xia, F., Sun, Y., Liu, H., Yan, L., Li, S., Jiang, D., Xu, M."Dichloroacetate induces protective autophagy in esophageal squamous carcinoma cells". Oncology Letters 14.3 (2017): 2765-2770.
Chicago
Jia, H., Wang, H., Xia, F., Sun, Y., Liu, H., Yan, L., Li, S., Jiang, D., Xu, M."Dichloroacetate induces protective autophagy in esophageal squamous carcinoma cells". Oncology Letters 14, no. 3 (2017): 2765-2770. https://doi.org/10.3892/ol.2017.6562