Tumor chemical suffocation therapy by dual respiratory inhibitions

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.

Automated summary

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.