Alexandre Tavartkiladze*, Gaiane Simonia, Ruite Lou, Pati Revazishvili, Dinara Kasradze, Maia Maisuradze, Rusudan Khutsishvili, Irine Andronikashvili, Pirdara Nozadze
Background: Glycolysis in tumor cells is a critical pathway for energy production and biomass accumulation, allowing rapid cell proliferation even in hypoxic conditions. This metabolic adaptation, known as the Warburg effect is characterized by glucose uptake via Glucose Transporter 1 (GLUT1) and the conversion of pyruvate to lactate by Lactate Dehydrogenase-A (LDH-A). Inhibition of glycolysis disrupts these pathways and may result in tumor regression. Phloretin, a natural GLUT1 inhibitor and melatonin, an agent known to downregulate LDH-A, show potential in glycolysis-targeted cancer therapy.
Materials and methods: A comparative study was conducted to evaluate the biochemical dynamics of glycolysis inhibition in patients with advanced Triple Negative Breast Cancer (TNBC) using phloretin and melatonin. Fifty-two women were divided into an advanced TNBC group (n=27) and a healthy control group (n=25). The effects of glycolysis inhibition were assessed by measuring levels of glucose, lactate, pyruvate and various metabolic intermediates, in addition to the expression of GLUT1 and LDH-A.
Results: Significant downregulation of glycolysis intermediates was observed in the treatment group, with a reduction in lactate production and an increase in oxidative phosphorylation markers. Tumor progression was notably suppressed and catabolic processes exceeded anabolic ones, as reflected by decreased glucose uptake, increased ketone body production and elevated amino acid catabolism.
Conclusion: The inhibition of glycolysis through combined use of Phloretin and melatonin effectively shifts the metabolic focus from glycolysis to oxidative phosphorylation, resulting in positive treatment dynamics for patients with advanced TNBC. These results highlight the potential for glycolytic inhibitors as part of a therapeutic strategy to target cancer metabolism.
Published Date: 2024-10-11; Received Date: 2024-09-10