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- Title
Dual inhibition of glycolysis and autophagy as a therapeutic strategy in the treatment of Ehrlich ascites carcinoma.
- Authors
Mansour, Mohammed A.; Ibrahim, Wafaa M.; Salama, Mona M.; Salama, Afrah F.
- 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.
- Subjects
EHRLICH ascites carcinoma; CELL metabolism; TREATMENT effectiveness; CELL size; ANIMAL models in research
- Publication
Journal of Biochemical & Molecular Toxicology, 2020, Vol 34, Issue 7, p1
- ISSN
1095-6670
- Publication type
Article
- DOI
10.1002/jbt.22498