Journal
CHEMICAL SCIENCE
Volume 12, Issue 22, Pages 7763-7769Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/d1sc00929j
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Funding
- National Natural Science Foundation of China [21835007, 52072394]
- Shanghai Science and Technology Committee Rising-Star Program [19QA1410100]
- Shanghai International Cooperation Project [20490714200]
- Key Research Program of Frontier Sciences, Chinese Academy of Sciences [ZDBS-LY-SLH029]
- Youth Innovation Promotion Association of the Chinese Academy of Science (2019)
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The study proposes a novel therapeutic strategy of tumor suffocation by concurrently suppressing glycolysis and mitochondrial oxidative phosphorylation through the co-deliveries of EDTA and rotenone into a glutathione-overexpressed tumor microenvironment. EDTA blocks glycolytic pathway by chelating magnesium ion to inhibit glycolytic enzymes, while rotenone inhibits mitochondrial OXPHOS. This work provides a new approach to treating tumors by inhibiting glucose metabolism, especially by de-functioning glycolytic enzymes.
The extraordinarily rapid growth of malignant tumors depends heavily on the glucose metabolism by the pathways of glycolysis and mitochondrial oxidative phosphorylation to generate adenosine 5 '-triphosphate (ATP) for maintaining cell proliferation and tumor growth. This study reports a tumor chemical suffocation therapeutic strategy by concurrently suppressing both glycolysis and mitochondrial oxidative phosphorylation (OXPHOS) via the co-deliveries of EDTA and rotenone into a glutathione (GSH)-overexpressed tumor microenvironment. EDTA is to block the glycolytic pathway through inhibiting the activity of glycolytic enzymes via the chelation of magnesium ion, a co-worker of glycolytic enzymes, despite the presence of Ca2+. Meanwhile rotenone is to inhibit the mitochondrial OXPHOS. This work provides a novel tumor suffocation strategy by the co-deliveries of glucose metabolism inhibitors, especially by de-functioning glycolytic enzymes via eliminating their co-worker magnesium.
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