Anticancer research · 2026
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.
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Miyashi Yuta, Mizuta Kohei, Ishiguro Tomoyuki, Han Qinghong, Li Shukuan, Kang Byung Mo, Kim Jin Soo, Bouvet Michael, Tome Yasunori, Nishida Kotaro, Hoffman Robert M
Аннотация
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.
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.