Work

Lactate does not replace glucose for maintaining the viability of mouse and human glioma cells

Year: 2025

Type: article

Abstract: Objectives Aerobic lactic acid fermentation (the “Warburg effect”) is associated with OxPhos insufficiency and altered energy metabolism in most cancers. Whether lactate is a major fuel in cancer cells remains debated. This study investigated whether lactate could serve as a metabolic fuel in glioma cells and replace glucose to support viability. Methods A bioluminescence ATP assay and calcein-AM/EthD-III double-staining were used to measure ATP content and viability in mouse (VM-M3, CT-2A) and human (U-87MG) glioma cells differing in cell biology and genetic background. Viability was assessed in thioglycollate-elicited peritoneal macrophages (TPMs) from VM/Dk and C57BL/6J mice, used as syngeneic non-neoplastic controls for VM-M3 and CT-2A, respectively. Oxygen consumption rate (OCR) was determined using the Resipher system. Results Lactate alone failed to sustain ATP content and viability in all glioma cell lines. ATP content and viability were lower in cancer cells cultured in glutamine and lactate than in glutamine and glucose. In contrast, lactate alone sustained >45 % viability in both non-neoplastic TPMs. Viability was similar between TPMs cultured in glutamine and lactate and in glutamine and glucose. Lactate increased OCR and viability in human U-87MG but only under severe glucose restriction. A low dose (0.25 mM) of the glycolysis inhibitor 2-deoxy-D-glucose abolished both increases. Conclusions Our results suggest non-neoplastic mouse TPMs utilize lactate more effectively than mouse glioma cells. Moreover, lactate utilization was glycolysis-dependent in U-87MG, based on sensitivity to 2-deoxy-D-glucose. The data do not support lactate as a major oxidative fuel for viability in these mouse and human glioma cells.

Source: ONCOLOGIE

DOI: 10.1515/oncologie-2025-0306