Dichloroacetate induces protective autophagy in esophageal squamous carcinoma cells

Jia, Hongyu; Wang, Henan; Xia, Fengyu; Sun, Yan; Liu, Hongli; Yan, Lili; Li, Shanshan; Jiang, Dong‑Chun; Xu, Meimei

doi:10.3892/ol.2017.6562

Cited by 10 publications

(2 citation statements)

References 23 publications

(22 reference statements)

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“…Various naturally occurring compounds have also been explored therapeutically in esophageal cancer. Resveratrol is a phytoalexin found in red wine and various foods that has been demonstrated to have anti-tumor effects in human cancer [87]. In the ESCC cell lines EC109, EC9706, and K562, resveratrol induced sub-G1 cell cycle arrest and apoptosis [88].…”

Section: Roles For Autophagy In Esophageal Cancer Responses To Thementioning

confidence: 99%

Roles for Autophagy in Esophageal Carcinogenesis: Implications for Improving Patient Outcomes

Saxena

Klochkova

Murray

et al. 2019

Cancers

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Esophageal cancer is among the most aggressive forms of human malignancy with five-year survival rates of <20%. Autophagy is an evolutionarily conserved catabolic process that degrades and recycles damaged organelles and misfolded proteins to maintain cellular homeostasis. While alterations in autophagy have been associated with carcinogenesis across tissues, cell type- and context-dependent roles for autophagy have been reported. Herein, we review the current knowledge related to autophagy in esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC), the two most common subtypes of esophageal malignancy. We explore roles for autophagy in the development and progression of ESCC and EAC. We then continue to discuss molecular markers of autophagy as they relate to esophageal patient outcomes. Finally, we summarize current literature examining roles for autophagy in ESCC and EAC response to therapy and discuss considerations for the potential use of autophagy inhibitors as experimental therapeutics that may improve patient outcomes in esophageal cancer.

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Section: Roles For Autophagy In Esophageal Cancer Responses To Thementioning

confidence: 99%

Roles for Autophagy in Esophageal Carcinogenesis: Implications for Improving Patient Outcomes

Saxena

Klochkova

Murray

et al. 2019

Cancers

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“…Although DCA is considered as a promising antitumor drug, there is some heterogeneity of its antitumor action [3,[6][7][8]. As one of the ways of strengthening its antitumor efficiency as well as reducing its possible toxicity risks the combination DCA with traditional chemotherapeutic drugs or other modifiers of the tumor cell energy metabolism is exploited [9][10][11].…”

mentioning

confidence: 99%

Tumor microenvironment changes tumor cell sensitivity to action of energy metabolism modifiers

et al. 2023

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Summary. Background: Taking into account differences in the bioenergetics between malignant and normal cells a search of antitumor drugs among the modifiers of tumor metabolism has a reasonable excuse. Earlier it was found that the cytotoxic/cytostatic action of sodium dichloroacetate (DCA) against Lewis lung carcinoma (LLC) cells in vitro was enhanced in the case of its combination with metformin (MTF). Aim: To study the antitumor action of DCA in combination with MTF against LLC in vivo. Materials and Methods: LLC/R9, a low metastatic variant of LLC cells, was used. LLC/R9 bearing mice were treated with MTF (at a total dose 0.15 g/kg b.w.) alone or in combination with DCA (at a total dose of 0.75 g/kg b.w.). LLC/R9 growth kinetics and the primary tumor growth and metastasis indices on the 23rd day after tumor cell inoculation were evaluated by routine procedures. The state of the electron transport chain of mitochondria in tumor cells was studied using electron paramagnetic resonance. The content of lactate and glucose in blood plasma from mice was measured by enzymatic methods using biochemical analyzer. The number of tumor-associated macrophages (TAMs) and their distribution by M1/M2 phenotype were estimated by flow cytometry using antibodies against CD68 and CD206. Results: In LLC/R9-bearing mice treated with DCA in combination with MTF, tumor growth and metastasis indices, as well as circulating glucose and lactate levels were not significantly different from those in the control group. The level of nitrosylation of non-heme and heme proteins and the content of iron-sulfur centers in the mitochondria of tumor cells in LLC/R9-bearing mice administered with DCA in combination with MTF did not also differ from the corresponding indices in control. Instead, in tumors treated with MTF alone and in combination with DCA the total CD68+ TAMs count was almost 27% (p < 0.05) and 43% lower (p < 0.05) correspondingly than that in control, but this decrease was not accompanied by redistribution of CD68+/CD206+ and CD68+/D206- subsets. Conclusion: DCA in combination with MTF, at least in doses applied, did not affect LLC/R9 growth and metastasis in vivo. The complete absence of an antitumor effect of DCA in combination with MTF was simultaneously associated with the absence of significant changes in the functional state of electron transport chain of mitochondria in tumor cells, circulating glucose and lactate levels, and the decrease of the TAMs amount in tumors. It suggests that the antitumor activity of DCA and MTF could be determined by both their local effects within a tumor and their multiple systemic impacts.

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Melatonin inhibits Warburg-dependent cancer by redirecting glucose oxidation to the mitochondria: a mechanistic hypothesis

Reíter

Sharma

et al. 2020

Cell. Mol. Life Sci.

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Dichloroacetate induces protective autophagy in esophageal squamous carcinoma cells

Cited by 10 publications

References 23 publications

Roles for Autophagy in Esophageal Carcinogenesis: Implications for Improving Patient Outcomes

Roles for Autophagy in Esophageal Carcinogenesis: Implications for Improving Patient Outcomes

Tumor microenvironment changes tumor cell sensitivity to action of energy metabolism modifiers

Melatonin inhibits Warburg-dependent cancer by redirecting glucose oxidation to the mitochondria: a mechanistic hypothesis

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