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To buffer the oxidative stress generated by rapid growth, division, and metabolic abnormalities, cancer cells have a higher demand for glutathione than normal cells, which leads homocysteine to favor the trans-sulfuration pathway over methionine regeneration ( -synthase (CBS) activity while reducing MAT activity, worsening methionine and SAM deficiency ( 3 Antitumor mechanisms of methionine restriction 3.1 Methionine restriction exerts antitumor effects by influencing epigenetic regulation In the field of cancer epigenetics, DNA methylation exhibits dual dysregulation characterized by genome-wide hypomethylation and specific hypermethylation of approximately 6070% of gene promoters containing Cytosine-phosphate-Guanine (CpG) islands, particularly those related to tumor suppressor genes, leading to their transcriptional silencing ( MR in gastric cancer cells results in decreased expression of the long non-coding RNA plasmacytoma variant translocation 1 (lncRNA PVT1) ( Furthermore, MET directly regulates the methylation modifications of DNA and histones via metabolic processes