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Here, we report that parthanatos, a kind of poly (ADP\u2010ribose) polymerase\u20101 (PARP1) dependent but caspase\u2010independent programmed cell death, does occur in two gastric cancer cell lines (MKN28 and MGC803) under glucose\u2010deprived conditions. Lactate prevented the glucose deprivation\u2010induced parthanatos in an acid\u2010independent manner. In addition, glucose deprivation increased intracellular reactive oxygen species (ROS) generation, whereas lactate reduces ROS levels by promoting NADPH generation. AG120, a selective inhibitor of isocitrate dehydrogenase 1 (IDH1) that catalyzes cytosolic NADPH generation, effectively eliminated the effect of lactate on NADPH generation and reversed the protective effect of lactate on glucose deprivation\u2010induced parthanatos. Similar effects were also observed when lactate dehydrogenase B (LDHB) was knocked down. Our findings reveal that lactate prevents glucose deprivation\u2010induced parthanatos in gastric cancer cells by alleviating intracellular oxidative stress, reflecting a new mechanism by which lactate facilitates the adaptation of tumor cells to the nutrient\u2010deficient tumor microenvironment and promotes tumor development.<\/jats:p>","DOI":"10.1002\/cbin.70064","type":"journal-article","created":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T04:40:36Z","timestamp":1754023236000},"page":"1441-1453","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Lactate Prevents Glucose Deprivation\u2010Induced Parthanatos in Gastric Cancer Cells Through Alleviating Intracellular Reactive Oxygen Species"],"prefix":"10.1002","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4303-668X","authenticated-orcid":false,"given":"Dun","family":"Niu","sequence":"first","affiliation":[{"name":"Hunan Provincial Key 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