The Glucose and Glutamine Requirements of Cancer and Normal Cells Do Not Distinguish Them, in Contrast to Their Methionine Requirement, Suggesting the Warburg Effect Is Not a Cancer Paradigm

Background/Aim: In the present study we compared the glucose and glutamine requirements of cancer and normal cells to determine if the Warburg effect is cancer specific. Materials and Methods: 143B human osteosarcoma, HT1080 human fibrosarcoma, HCT116 human colon cancer and normal Hs27 human fibroblasts were cultured in Dulbecco’s modified Eagle’s medium (DMEM) with and without glucose; with and without glutamine; or with and without methionine. The EC₅₀ of glucose, glutamine and methionine was compared in cancer and normal cells. Co-culture of Hs27 normal fibroblast with each cancer cell line was performed by using 12-well plates with and without glucose or methionine. Cell viability was determined with the WST-8 viability reagent, by phase-contrast microscopy or fluorescence microscopy. Results: The EC₅₀ of glucose for the three cancer cell lines ranged from 0.54 to 4.88 mM. The EC₅₀ of glucose for Hs27 normal fibroblasts was 0.35 mM, which was not significantly lower than in HCT116 cells (p=0.2225). The EC₅₀ for glutamine ranged from 0.15 to 0.54 mM for the cancer-cell lines and 0.24 mM for normal fibroblasts, which did not distinguish normal from cancer cells. For comparison the EC₅₀ of cancer cells for methionine ranged from 3.8 μM to 21.4 μM while for normal fibroblasts the EC₅₀ for methionine was 2.3 μM, which was significantly lower than in all the cancer cell lines (p<0.0167). In co-culture of cancer and normal fibroblasts, glucose-free or glutamine-free medium resulted in loss of cell viability by day 7 for both the cancer and normal cells. In contrast, in methionine-free medium, the normal fibroblasts were alive and healthy at day 7. Conclusion: The Warburg effect of glucose and glutamine addiction is not cancer specific in comparison to methionine addiction (Hoffman effect), which is cancer specific, suggesting the Warburg effect is not a cancer paradigm.