{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T19:12:35Z","timestamp":1793041955613,"version":"4.5.0"},"reference-count":22,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Background\/aim<\/jats:title>\n                    <jats:p>Many studies in the present century have stated that restriction of serine is a cancer-specific vulnerability. The present study aimed to determine whether restriction of serine, compared to restriction of methionine, distinguishes cancer and normal cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>\n                      143B-RFP osteosarcoma cells, HT1080-RFP fibrosarcoma cells, HCT116-GFP colon-cancer cells, and Hs27 normal fibroblasts were used in the present study. All cells are of human origin. Cancer and normal cells were cultured in RPMI-1640 medium without serine and glycine for serine\/glycine restriction, and in Dulbecco\u2019s modified Eagle\u2019s medium without methionine for methionine restriction, each supplemented with 10% dialyzed fetal bovine serum. Cancer and normal cells were cultured in 96-well plates at 2 \u00d7 10\n                      <jats:sup>3<\/jats:sup>\n                      cells\/well. Serine, glycine, and methionine were added back as controls. Cell viability was measured with the WST-8 cell-viability reagent to establish dose-response curves for serine (with or without glycine) and for methionine in cancer and normal cells. Each cancer cell line was also co-cultured with Hs27 normal fibroblasts in 12-well plates. Each cell type was evaluated by phase-contrast and GFP\/RFP fluorescence microscopy to determine the effects of serine\/glycine restriction or methionine restriction.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Serine restriction alone did not distinguish cancer and normal cells. Both 143B osteosarcoma and Hs27 normal fibroblasts maintained approximately 100% viability without serine in glycine-containing medium. The HT1080-RFP and HCT116-GFP cancer cells lost approximately 40% of their viability without serine and showed increasing viability with increasing serine concentration. When both serine and glycine were restricted, Hs27 fibroblasts lost approximately 20% viability, whereas all cancer cells lost about 40% viability. Neither serine restriction nor serine\/glycine restriction could lower the viability of cancer cells to 50% of control. In co-culture, the removal of serine and glycine still left many cancer cells viable. In contrast, methionine removal caused a much greater reduction in cancer-cell viability than removal of serine\/glycine. Hs27 normal fibroblasts survived well under both serine\/glycine and methionine restriction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Serine restriction and serine\/glycine restriction are not as cancer-specific as methionine restriction.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1931323","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T12:27:11Z","timestamp":1788265631000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Direct comparison of serine restriction on the viability of normal and cancer cells demonstrates that methionine restriction is more cancer specific"],"prefix":"10.3389","volume":"16","author":[{"given":"Yuta","family":"Miyashi","sequence":"first","affiliation":[{"name":"AntiCancer, Inc.","place":["San Diego, CA, United 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