Dual inhibition of glycolysis and autophagy as a therapeutic strategy in the treatment of Ehrlich ascites carcinoma

Journal article


Mansour, MA, Ibrahim, WM, Salama, MM and Salama, AF (2020). Dual inhibition of glycolysis and autophagy as a therapeutic strategy in the treatment of Ehrlich ascites carcinoma. Journal of Biochemical and Molecular Toxicology. 34 (7). https://doi.org/10.1002/jbt.22498
AuthorsMansour, MA, Ibrahim, WM, Salama, MM and Salama, AF
Abstract

Cancer cells have extra biosynthetic demands to sustain cell growth and redox homeostasis. Glycolysis and autophagy are crucial to fuel and recycle these biosynthetic demands. This plasticity of cancer cell metabolism participates in therapy resistances. The current study was designed to assess the therapeutic efficacy of dual targeting of glycolysis and autophagy in cancer. Using 3‐bromopyruvate (3‐BP; antiglycolytic inhibitor) and hydroxychloroquine (HCQ; autophagy inhibitor), we demonstrate their antitumor activity in Ehrlich ascites carcinoma (EAC)‐bearing mice. A combination of 3‐BP and HCQ significantly decreases tumor ascitic volume and cell count as compared with the EAC group and individual treatment groups. The enhanced antitumor activity is accompanied by hexokinase inactivation, inhibition of cellular protective autophagy, elevated antioxidant activity, and reduced oxidative stress levels. Together, these results suggest targeting both pathways in cancer as an effective therapeutic strategy. Further studies are required to validate this strategy in different cancer models and preclinical trials.

This is the peer reviewed version of the following article: Mansour, MA, Ibrahim, WM, Salama, MM, Salama, AF. Dual inhibition of glycolysis and autophagy as a therapeutic strategy in the treatment of Ehrlich ascites carcinoma. J Biochem Mol Toxicol. 2020; 34:e22498. , which has been published in final form at https://doi.org/10.1002/jbt.22498. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.

Keywords3‐bromopyruvate; autophagy; glycolysis; hexokinase 2; hydroxychloroquine
Year2020
JournalJournal of Biochemical and Molecular Toxicology
Journal citation34 (7)
PublisherWiley
ISSN1095-6670
Digital Object Identifier (DOI)https://doi.org/10.1002/jbt.22498
Publication dates
Print20 Mar 2020
Publication process dates
Accepted20 Feb 2020
Deposited05 Aug 2020
Accepted author manuscript
License
File Access Level
Open
Page rangee22498-e22498
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