Huaier suppresses lung cancer by simultaneously and independently inhibiting the antioxidant pathway SLC7A11/GPX4 while enhancing ferritinophagy
Abstract Huaier (Trametes Robiniophila Murr), a traditional Chinese medicine, has emerged as a promising therapeutic agent against cancers in clinical settings, yet its underlying mechanisms remain elusive. In this study, we demonstrate that Huaier effectively suppresses lung cancer by inducing ferr...
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| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-07-01
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| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-025-02598-3 |
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| _version_ | 1849238090698194944 |
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| author | Xingxing Shi Kun Liu Yuchang Tian Xinyi Bi Junkai Zhang Fengyi Ma Wensheng Wei Tongbiao Zhao |
| author_facet | Xingxing Shi Kun Liu Yuchang Tian Xinyi Bi Junkai Zhang Fengyi Ma Wensheng Wei Tongbiao Zhao |
| author_sort | Xingxing Shi |
| collection | DOAJ |
| description | Abstract Huaier (Trametes Robiniophila Murr), a traditional Chinese medicine, has emerged as a promising therapeutic agent against cancers in clinical settings, yet its underlying mechanisms remain elusive. In this study, we demonstrate that Huaier effectively suppresses lung cancer by inducing ferroptosis. Mechanistically, Huaier simultaneously and independently downregulates the antioxidant pathway SLC7A11/GPX4 and elevates intracellular iron levels through NCOA4-mediated ferritinophagy degradation of FTH1 in lung cancer cells. Both the iron chelator deferoxamine (DFO) and the ferroptosis inhibitor ferrostatin-1 (Fer-1) mitigate Huaier-induced cell death. In both urethane-induced lung tumorigenesis models and cell-derived xenograft (CDX) models, Huaier significantly inhibits tumor progression by inducing ferroptosis, which can be counteracted by SRS16-86. Our study uncovers a novel mechanism by which Huaier induces ferroptosis to suppress lung cancer, underscoring its potential as a therapeutic agent for lung cancer or as part of a combination therapy strategy. |
| format | Article |
| id | doaj-art-5c51aa27ea6140f7addbe625263f1f5d |
| institution | Kabale University |
| issn | 2058-7716 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death Discovery |
| spelling | doaj-art-5c51aa27ea6140f7addbe625263f1f5d2025-08-20T04:01:47ZengNature Publishing GroupCell Death Discovery2058-77162025-07-0111111110.1038/s41420-025-02598-3Huaier suppresses lung cancer by simultaneously and independently inhibiting the antioxidant pathway SLC7A11/GPX4 while enhancing ferritinophagyXingxing Shi0Kun Liu1Yuchang Tian2Xinyi Bi3Junkai Zhang4Fengyi Ma5Wensheng Wei6Tongbiao Zhao7State Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of SciencesState Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of SciencesState Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of SciencesState Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of SciencesState Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of SciencesState Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of SciencesBiomedical Pioneering Innovation Center, Peking-Tsinghua Center for Life Sciences, Peking University Genome Editing Research Center, State Key Laboratory of Gene Function and Modulation Research, School of Life Sciences, Peking UniversityState Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of SciencesAbstract Huaier (Trametes Robiniophila Murr), a traditional Chinese medicine, has emerged as a promising therapeutic agent against cancers in clinical settings, yet its underlying mechanisms remain elusive. In this study, we demonstrate that Huaier effectively suppresses lung cancer by inducing ferroptosis. Mechanistically, Huaier simultaneously and independently downregulates the antioxidant pathway SLC7A11/GPX4 and elevates intracellular iron levels through NCOA4-mediated ferritinophagy degradation of FTH1 in lung cancer cells. Both the iron chelator deferoxamine (DFO) and the ferroptosis inhibitor ferrostatin-1 (Fer-1) mitigate Huaier-induced cell death. In both urethane-induced lung tumorigenesis models and cell-derived xenograft (CDX) models, Huaier significantly inhibits tumor progression by inducing ferroptosis, which can be counteracted by SRS16-86. Our study uncovers a novel mechanism by which Huaier induces ferroptosis to suppress lung cancer, underscoring its potential as a therapeutic agent for lung cancer or as part of a combination therapy strategy.https://doi.org/10.1038/s41420-025-02598-3 |
| spellingShingle | Xingxing Shi Kun Liu Yuchang Tian Xinyi Bi Junkai Zhang Fengyi Ma Wensheng Wei Tongbiao Zhao Huaier suppresses lung cancer by simultaneously and independently inhibiting the antioxidant pathway SLC7A11/GPX4 while enhancing ferritinophagy Cell Death Discovery |
| title | Huaier suppresses lung cancer by simultaneously and independently inhibiting the antioxidant pathway SLC7A11/GPX4 while enhancing ferritinophagy |
| title_full | Huaier suppresses lung cancer by simultaneously and independently inhibiting the antioxidant pathway SLC7A11/GPX4 while enhancing ferritinophagy |
| title_fullStr | Huaier suppresses lung cancer by simultaneously and independently inhibiting the antioxidant pathway SLC7A11/GPX4 while enhancing ferritinophagy |
| title_full_unstemmed | Huaier suppresses lung cancer by simultaneously and independently inhibiting the antioxidant pathway SLC7A11/GPX4 while enhancing ferritinophagy |
| title_short | Huaier suppresses lung cancer by simultaneously and independently inhibiting the antioxidant pathway SLC7A11/GPX4 while enhancing ferritinophagy |
| title_sort | huaier suppresses lung cancer by simultaneously and independently inhibiting the antioxidant pathway slc7a11 gpx4 while enhancing ferritinophagy |
| url | https://doi.org/10.1038/s41420-025-02598-3 |
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