Exogenous dihomo-γ-linolenic acid triggers ferroptosis via ACSL4-mediated lipid metabolic reprogramming in acute myeloid leukemia cells
Ferroptosis is a novel type of programmed cell death caused by excessive iron-dependent lipid peroxidation. According to various studies, there may be a link between ferroptosis and lipid metabolism. However, few studies have been reported on the lipid metabolism of ferroptosis in acute myeloid leuk...
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| Language: | English |
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Elsevier
2025-02-01
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| Series: | Translational Oncology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S193652332400353X |
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| author | Xiandong Jiang Yingying Huang Xiaoying Hong Wei Wu Yanfeng Lin Liping Lin Yan Xue Donghong Lin |
| author_facet | Xiandong Jiang Yingying Huang Xiaoying Hong Wei Wu Yanfeng Lin Liping Lin Yan Xue Donghong Lin |
| author_sort | Xiandong Jiang |
| collection | DOAJ |
| description | Ferroptosis is a novel type of programmed cell death caused by excessive iron-dependent lipid peroxidation. According to various studies, there may be a link between ferroptosis and lipid metabolism. However, few studies have been reported on the lipid metabolism of ferroptosis in acute myeloid leukemia (AML). Here, we analyzed the relationship between lipid metabolism and ferroptosis in AML cells to explore new clinical treatment strategies. This study found that 12 fatty acids were significantly changed in acute myeloid leukemia cell ferroptosis, including dihomo-γ-linolenic acid (DGLA), arachidonic acid (AA), docosahexaenoic acid (DHA), etc. Exogenous DGLA substantially increases the sensitivity to ferroptosis and induces ferroptosis alone in AML cells. In addition, acyl-CoA synthetase long-chain family member 4 (ACSL4) knockout significantly inhibited DGLA-induced AML cells ferroptosis, and ACSL4 regulates DGLA-associated lipid synthesis to affect the sensitivity of AML cells to ferroptosis. Collectively, our studies indicate that a DGLA-enriched diet significantly restricted the growth of leukemia cells as well as induced ferroptosis in vivo. |
| format | Article |
| id | doaj-art-a7adc41be4564046945bfb118a674001 |
| institution | Kabale University |
| issn | 1936-5233 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Translational Oncology |
| spelling | doaj-art-a7adc41be4564046945bfb118a6740012025-01-22T05:41:23ZengElsevierTranslational Oncology1936-52332025-02-0152102227Exogenous dihomo-γ-linolenic acid triggers ferroptosis via ACSL4-mediated lipid metabolic reprogramming in acute myeloid leukemia cellsXiandong Jiang0Yingying Huang1Xiaoying Hong2Wei Wu3Yanfeng Lin4Liping Lin5Yan Xue6Donghong Lin7Department of Laboratory Medicine, The School of Medical Technology and Engineering, Fujian Medical University, Fuzhou 350122, China; Key Laboratory of Clinical Laboratory Technology for Precision Medicine (Fujian Medical University), Fujian Province University, Fuzhou 350122, ChinaDepartment of Laboratory Medicine, The School of Medical Technology and Engineering, Fujian Medical University, Fuzhou 350122, China; Key Laboratory of Clinical Laboratory Technology for Precision Medicine (Fujian Medical University), Fujian Province University, Fuzhou 350122, ChinaDepartment of Laboratory Medicine, The School of Medical Technology and Engineering, Fujian Medical University, Fuzhou 350122, China; Key Laboratory of Clinical Laboratory Technology for Precision Medicine (Fujian Medical University), Fujian Province University, Fuzhou 350122, ChinaDepartment of Laboratory Medicine, The School of Medical Technology and Engineering, Fujian Medical University, Fuzhou 350122, China; Medical Technology Experimental Teaching Center, The School of Medical Technology and Engineering, Fujian Medical University, Fuzhou 350122, ChinaMedical Technology Experimental Teaching Center, The School of Medical Technology and Engineering, Fujian Medical University, Fuzhou 350122, China; Key Laboratory of Clinical Laboratory Technology for Precision Medicine (Fujian Medical University), Fujian Province University, Fuzhou 350122, ChinaDepartment of Laboratory Medicine, The School of Medical Technology and Engineering, Fujian Medical University, Fuzhou 350122, China; Key Laboratory of Clinical Laboratory Technology for Precision Medicine (Fujian Medical University), Fujian Province University, Fuzhou 350122, ChinaMedical Technology Experimental Teaching Center, The School of Medical Technology and Engineering, Fujian Medical University, Fuzhou 350122, China; Key Laboratory of Clinical Laboratory Technology for Precision Medicine (Fujian Medical University), Fujian Province University, Fuzhou 350122, China; Corresponding authors.Department of Laboratory Medicine, The School of Medical Technology and Engineering, Fujian Medical University, Fuzhou 350122, China; Key Laboratory of Clinical Laboratory Technology for Precision Medicine (Fujian Medical University), Fujian Province University, Fuzhou 350122, China; Corresponding authors.Ferroptosis is a novel type of programmed cell death caused by excessive iron-dependent lipid peroxidation. According to various studies, there may be a link between ferroptosis and lipid metabolism. However, few studies have been reported on the lipid metabolism of ferroptosis in acute myeloid leukemia (AML). Here, we analyzed the relationship between lipid metabolism and ferroptosis in AML cells to explore new clinical treatment strategies. This study found that 12 fatty acids were significantly changed in acute myeloid leukemia cell ferroptosis, including dihomo-γ-linolenic acid (DGLA), arachidonic acid (AA), docosahexaenoic acid (DHA), etc. Exogenous DGLA substantially increases the sensitivity to ferroptosis and induces ferroptosis alone in AML cells. In addition, acyl-CoA synthetase long-chain family member 4 (ACSL4) knockout significantly inhibited DGLA-induced AML cells ferroptosis, and ACSL4 regulates DGLA-associated lipid synthesis to affect the sensitivity of AML cells to ferroptosis. Collectively, our studies indicate that a DGLA-enriched diet significantly restricted the growth of leukemia cells as well as induced ferroptosis in vivo.http://www.sciencedirect.com/science/article/pii/S193652332400353XDihomo-γ-linolenic acidFerroptosisACSL4Lipid metabolicAcute myeloid leukemia |
| spellingShingle | Xiandong Jiang Yingying Huang Xiaoying Hong Wei Wu Yanfeng Lin Liping Lin Yan Xue Donghong Lin Exogenous dihomo-γ-linolenic acid triggers ferroptosis via ACSL4-mediated lipid metabolic reprogramming in acute myeloid leukemia cells Translational Oncology Dihomo-γ-linolenic acid Ferroptosis ACSL4 Lipid metabolic Acute myeloid leukemia |
| title | Exogenous dihomo-γ-linolenic acid triggers ferroptosis via ACSL4-mediated lipid metabolic reprogramming in acute myeloid leukemia cells |
| title_full | Exogenous dihomo-γ-linolenic acid triggers ferroptosis via ACSL4-mediated lipid metabolic reprogramming in acute myeloid leukemia cells |
| title_fullStr | Exogenous dihomo-γ-linolenic acid triggers ferroptosis via ACSL4-mediated lipid metabolic reprogramming in acute myeloid leukemia cells |
| title_full_unstemmed | Exogenous dihomo-γ-linolenic acid triggers ferroptosis via ACSL4-mediated lipid metabolic reprogramming in acute myeloid leukemia cells |
| title_short | Exogenous dihomo-γ-linolenic acid triggers ferroptosis via ACSL4-mediated lipid metabolic reprogramming in acute myeloid leukemia cells |
| title_sort | exogenous dihomo γ linolenic acid triggers ferroptosis via acsl4 mediated lipid metabolic reprogramming in acute myeloid leukemia cells |
| topic | Dihomo-γ-linolenic acid Ferroptosis ACSL4 Lipid metabolic Acute myeloid leukemia |
| url | http://www.sciencedirect.com/science/article/pii/S193652332400353X |
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