Naringenin induces ferroptosis in osteosarcoma cells through the STAT3-MGST2 signaling pathway
Osteosarcoma is a common malignant tumor found in adolescents, characterized by a high metastatic potential and poor prognosis, but it is sensitive to radiotherapy and chemotherapy. Ferroptosis is a novel form of regulated cell death induced by excessive iron accumulation, leading to lipid peroxidat...
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| Language: | English |
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Elsevier
2025-02-01
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| Series: | Journal of Bone Oncology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2212137424001374 |
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| author | Yingang Li Xizhuang Bai |
| author_facet | Yingang Li Xizhuang Bai |
| author_sort | Yingang Li |
| collection | DOAJ |
| description | Osteosarcoma is a common malignant tumor found in adolescents, characterized by a high metastatic potential and poor prognosis, but it is sensitive to radiotherapy and chemotherapy. Ferroptosis is a novel form of regulated cell death induced by excessive iron accumulation, leading to lipid peroxidation that results in cellular dysfunction and death. Naringenin is a flavonoid known for its anti-cancer properties, yet its role in osteosarcoma has not been thoroughly studied. In this study, we found that naringenin significantly reduced the viability of osteosarcoma cells while increasing the accumulation of reactive oxygen species (ROS), iron overload, and the excessive expression of malondialdehyde (MDA). Bioinformatics analysis revealed that microsomal glutathione S-transferase 2 (MGST2) is highly expressed in osteosarcoma cells. Silencing MGST2 decreased the proliferation, migration, and invasion of these cells and enhanced their sensitivity to ferroptosis. Mechanistically, signal transducer and activator of transcription 3 (STAT3) binds to the MGST2 promoter, promoting its transcription. Naringenin inhibits STAT3, blocking the expression of MGST2, while the STAT3 agonist Colivelin reverses this effect. In vivo experiments further confirmed that naringenin inhibited tumor growth in subcutaneous xenograft models and exhibited good biosafety. In summary, our study demonstrates that naringenin induces ferroptosis in osteosarcoma cells through the STAT3-MGST2 signaling pathway, providing a promising strategy for osteosarcoma treatment. |
| format | Article |
| id | doaj-art-6de16dd805c74dd88e02e6331474fdc8 |
| institution | Kabale University |
| issn | 2212-1374 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Bone Oncology |
| spelling | doaj-art-6de16dd805c74dd88e02e6331474fdc82025-01-20T04:17:25ZengElsevierJournal of Bone Oncology2212-13742025-02-0150100657Naringenin induces ferroptosis in osteosarcoma cells through the STAT3-MGST2 signaling pathwayYingang Li0Xizhuang Bai1China Medical University, Shenyang, Liaoning, China; Liaoning Provincial People’s Hospital, Shenyang, Liaoning, ChinaLiaoning Provincial People’s Hospital, Shenyang, Liaoning, China; Corresponding author.Osteosarcoma is a common malignant tumor found in adolescents, characterized by a high metastatic potential and poor prognosis, but it is sensitive to radiotherapy and chemotherapy. Ferroptosis is a novel form of regulated cell death induced by excessive iron accumulation, leading to lipid peroxidation that results in cellular dysfunction and death. Naringenin is a flavonoid known for its anti-cancer properties, yet its role in osteosarcoma has not been thoroughly studied. In this study, we found that naringenin significantly reduced the viability of osteosarcoma cells while increasing the accumulation of reactive oxygen species (ROS), iron overload, and the excessive expression of malondialdehyde (MDA). Bioinformatics analysis revealed that microsomal glutathione S-transferase 2 (MGST2) is highly expressed in osteosarcoma cells. Silencing MGST2 decreased the proliferation, migration, and invasion of these cells and enhanced their sensitivity to ferroptosis. Mechanistically, signal transducer and activator of transcription 3 (STAT3) binds to the MGST2 promoter, promoting its transcription. Naringenin inhibits STAT3, blocking the expression of MGST2, while the STAT3 agonist Colivelin reverses this effect. In vivo experiments further confirmed that naringenin inhibited tumor growth in subcutaneous xenograft models and exhibited good biosafety. In summary, our study demonstrates that naringenin induces ferroptosis in osteosarcoma cells through the STAT3-MGST2 signaling pathway, providing a promising strategy for osteosarcoma treatment.http://www.sciencedirect.com/science/article/pii/S2212137424001374OsteosarcomaFerroptosisNaringeninSTAT3MGST2 |
| spellingShingle | Yingang Li Xizhuang Bai Naringenin induces ferroptosis in osteosarcoma cells through the STAT3-MGST2 signaling pathway Journal of Bone Oncology Osteosarcoma Ferroptosis Naringenin STAT3 MGST2 |
| title | Naringenin induces ferroptosis in osteosarcoma cells through the STAT3-MGST2 signaling pathway |
| title_full | Naringenin induces ferroptosis in osteosarcoma cells through the STAT3-MGST2 signaling pathway |
| title_fullStr | Naringenin induces ferroptosis in osteosarcoma cells through the STAT3-MGST2 signaling pathway |
| title_full_unstemmed | Naringenin induces ferroptosis in osteosarcoma cells through the STAT3-MGST2 signaling pathway |
| title_short | Naringenin induces ferroptosis in osteosarcoma cells through the STAT3-MGST2 signaling pathway |
| title_sort | naringenin induces ferroptosis in osteosarcoma cells through the stat3 mgst2 signaling pathway |
| topic | Osteosarcoma Ferroptosis Naringenin STAT3 MGST2 |
| url | http://www.sciencedirect.com/science/article/pii/S2212137424001374 |
| work_keys_str_mv | AT yingangli naringenininducesferroptosisinosteosarcomacellsthroughthestat3mgst2signalingpathway AT xizhuangbai naringenininducesferroptosisinosteosarcomacellsthroughthestat3mgst2signalingpathway |