Lactate in ferroptosis regulation: A new perspective on tumor progression and therapy
Ferroptosis is a type of regulated cell death induced by iron-dependent lipid peroxidation, which is tightly regulated by metabolism. Lactate is a byproduct of glycolysis that regulates energy, fatty acid metabolism, and redox homeostasis as a fuel or signaling molecule. The role of lactate in ferro...
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| Language: | English |
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Elsevier
2025-08-01
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| Series: | Pharmacological Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S104366182500266X |
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| author | Nan Wu Xiaoqi Wei Shuang Yu Lina Yang Xiaowen Zhang |
| author_facet | Nan Wu Xiaoqi Wei Shuang Yu Lina Yang Xiaowen Zhang |
| author_sort | Nan Wu |
| collection | DOAJ |
| description | Ferroptosis is a type of regulated cell death induced by iron-dependent lipid peroxidation, which is tightly regulated by metabolism. Lactate is a byproduct of glycolysis that regulates energy, fatty acid metabolism, and redox homeostasis as a fuel or signaling molecule. The role of lactate in ferroptosis occurs under different contexts. Lactate promotes ferroptosis under non-tumoral conditions, whereas in the tumor microenvironment, it can lead to tumor cell resistance to ferroptosis, thereby promoting tumor proliferation, metastasis, and drug resistance. The specific molecular mechanisms underlying lactate-regulated ferroptosis involve polyunsaturated fatty acids metabolism, antioxidant systems, iron metabolism, and mitochondrial function by lactate or lactate-induced lactylation. In addition, nanomaterials containing LOX and/or inhibition of MCTs may be used to enhance tumor cell ferroptosis in various cancers by targeting lactate metabolism. In this review, we systematically summarize the role and mechanism of lactate in ferroptosis regulation in pathophysiology, particularly in tumor progression and therapy, which provides a new perspective on tumor progression and therapy. |
| format | Article |
| id | doaj-art-1e901e8d51de453aae40b1ea762fc6cc |
| institution | Kabale University |
| issn | 1096-1186 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Pharmacological Research |
| spelling | doaj-art-1e901e8d51de453aae40b1ea762fc6cc2025-08-20T03:55:49ZengElsevierPharmacological Research1096-11862025-08-0121810784110.1016/j.phrs.2025.107841Lactate in ferroptosis regulation: A new perspective on tumor progression and therapyNan Wu0Xiaoqi Wei1Shuang Yu2Lina Yang3Xiaowen Zhang4Department of Central Laboratory, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, PR China; Correspondence to: 155th North of Nanjing Street, Heping District, Shenyang, Liaoning 110001, PR China.Department of Central Laboratory, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, PR ChinaDepartment of Central Laboratory, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, PR ChinaDepartment of International Physical Examination Center, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, PR China; Correspondence to: 155th North of Nanjing Street, Heping District, Shenyang, Liaoning 110001, PR China.Department of Otolaryngology Head and Neck Surgery, Shengjing Hospital of China Medical University. Medical Research Center, Shengjing Hospital of China Medical University. Liaoning Key Laboratory of Research and Application of Animal Models for Environmental and Metabolic Diseases, Shenyang, Liaoning, PR China; Correspondence to: #36 Sanhao Street, Heping District, Shenyang, Liaoning 110004, PR China.Ferroptosis is a type of regulated cell death induced by iron-dependent lipid peroxidation, which is tightly regulated by metabolism. Lactate is a byproduct of glycolysis that regulates energy, fatty acid metabolism, and redox homeostasis as a fuel or signaling molecule. The role of lactate in ferroptosis occurs under different contexts. Lactate promotes ferroptosis under non-tumoral conditions, whereas in the tumor microenvironment, it can lead to tumor cell resistance to ferroptosis, thereby promoting tumor proliferation, metastasis, and drug resistance. The specific molecular mechanisms underlying lactate-regulated ferroptosis involve polyunsaturated fatty acids metabolism, antioxidant systems, iron metabolism, and mitochondrial function by lactate or lactate-induced lactylation. In addition, nanomaterials containing LOX and/or inhibition of MCTs may be used to enhance tumor cell ferroptosis in various cancers by targeting lactate metabolism. In this review, we systematically summarize the role and mechanism of lactate in ferroptosis regulation in pathophysiology, particularly in tumor progression and therapy, which provides a new perspective on tumor progression and therapy.http://www.sciencedirect.com/science/article/pii/S104366182500266XLactateLactylationFerroptosisChemodynamic therapyTumor progression |
| spellingShingle | Nan Wu Xiaoqi Wei Shuang Yu Lina Yang Xiaowen Zhang Lactate in ferroptosis regulation: A new perspective on tumor progression and therapy Pharmacological Research Lactate Lactylation Ferroptosis Chemodynamic therapy Tumor progression |
| title | Lactate in ferroptosis regulation: A new perspective on tumor progression and therapy |
| title_full | Lactate in ferroptosis regulation: A new perspective on tumor progression and therapy |
| title_fullStr | Lactate in ferroptosis regulation: A new perspective on tumor progression and therapy |
| title_full_unstemmed | Lactate in ferroptosis regulation: A new perspective on tumor progression and therapy |
| title_short | Lactate in ferroptosis regulation: A new perspective on tumor progression and therapy |
| title_sort | lactate in ferroptosis regulation a new perspective on tumor progression and therapy |
| topic | Lactate Lactylation Ferroptosis Chemodynamic therapy Tumor progression |
| url | http://www.sciencedirect.com/science/article/pii/S104366182500266X |
| work_keys_str_mv | AT nanwu lactateinferroptosisregulationanewperspectiveontumorprogressionandtherapy AT xiaoqiwei lactateinferroptosisregulationanewperspectiveontumorprogressionandtherapy AT shuangyu lactateinferroptosisregulationanewperspectiveontumorprogressionandtherapy AT linayang lactateinferroptosisregulationanewperspectiveontumorprogressionandtherapy AT xiaowenzhang lactateinferroptosisregulationanewperspectiveontumorprogressionandtherapy |