Repurposed genipin targeting UCP2 exhibits antitumor activity through inducing ferroptosis in glioblastoma
Uncoupling protein-2 (UCP2) controls the antioxidant response and redox homeostasis in cancer and is considered a potent molecular target for cancer treatment. However, the specific mechanism of UCP2 inhibition and its role in glioblastoma...
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| Format: | Article |
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China Science Publishing & Media Ltd.
2024-11-01
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| Series: | Acta Biochimica et Biophysica Sinica |
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| Online Access: | https://www.sciengine.com/doi/10.3724/abbs.2024168 |
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| author | Dong Hao Sun Kaixuan Wang Xuejie Cui Meimei Ma Yaping Li Kexin Duan Wanli Zhang Hongxing Zhang Liying Sheng Zhimei He Maotao Zhang Baogang |
| author_facet | Dong Hao Sun Kaixuan Wang Xuejie Cui Meimei Ma Yaping Li Kexin Duan Wanli Zhang Hongxing Zhang Liying Sheng Zhimei He Maotao Zhang Baogang |
| author_sort | Dong Hao |
| collection | DOAJ |
| description | Uncoupling protein-2 (UCP2) controls the antioxidant response and redox homeostasis in cancer and is considered a potent molecular target for cancer treatment. However, the specific mechanism of UCP2 inhibition and its role in glioblastoma (GBM) have not yet been elucidated. Here, we attempt to identify a UCP2 inhibitor and study the underlying molecular mechanism in GBM. Bioinformatics analysis and immunohistochemistry are used to validate the high expression of UCP2 in GBM and its prognostic significance. Drug intervention and tumor xenograft experiments are conducted to determine the inhibitory effect of genipin, a UCP2 inhibitor, on UCP2. The mitochondrial membrane potential and key ferroptosis genes are examined to determine the occurrence of ferroptosis. High expression of UCP2 in GBM is associated with poor prognosis, and inhibiting UCP2 can alleviate the malignant behavior of GBM tumors. Genipin can downregulate the expression of GPX4 and upregulate the expression of ACSL4 by inhibiting UCP2, leading to ferroptosis and alleviating the malignant behavior of tumors. In summary, UCP2 is a potential therapeutic target for GBM. Genipin, which targets UCP2, effectively inhibits GBM development by inducing ferroptosis in vivo and in vitro. These findings indicate that genipin treatment based on UCP2 targeting has potential therapeutic applications with a clinical perspective for the treatment of GBM patients. |
| format | Article |
| id | doaj-art-4c081f2e4b614a79844d220c8808c985 |
| institution | OA Journals |
| issn | 1672-9145 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | China Science Publishing & Media Ltd. |
| record_format | Article |
| series | Acta Biochimica et Biophysica Sinica |
| spelling | doaj-art-4c081f2e4b614a79844d220c8808c9852025-08-20T01:55:33ZengChina Science Publishing & Media Ltd.Acta Biochimica et Biophysica Sinica1672-91452024-11-015740341410.3724/abbs.202416820d259ccRepurposed genipin targeting UCP2 exhibits antitumor activity through inducing ferroptosis in glioblastomaDong Hao0Sun Kaixuan1Wang Xuejie2Cui Meimei3Ma Yaping4Li Kexin5Duan Wanli6Zhang Hongxing7Zhang Liying8Sheng Zhimei9He Maotao10Zhang Baogang11["Department of Diagnostic Pathology, School of Basic Medical Sciences, Shandong Second Medical University, Weifang 261042, China"]["Department of Pathology, Affiliated Hospital of Shandong Second Medical University, Weifang 261041, China"]["Department of Diagnostic Pathology, School of Basic Medical Sciences, Shandong Second Medical University, Weifang 261042, China"]["Department of Diagnostic Pathology, School of Basic Medical Sciences, Shandong Second Medical University, Weifang 261042, China"]["Department of Diagnostic Pathology, School of Basic Medical Sciences, Shandong Second Medical University, Weifang 261042, China"]["Department of Diagnostic Pathology, School of Basic Medical Sciences, Shandong Second Medical University, Weifang 261042, China"]["Department of Diagnostic Pathology, School of Basic Medical Sciences, Shandong Second Medical University, Weifang 261042, China"]["Department of Diagnostic Pathology, School of Basic Medical Sciences, Shandong Second Medical University, Weifang 261042, China"]["Department of Diagnostic Pathology, School of Basic Medical Sciences, Shandong Second Medical University, Weifang 261042, China"]["Department of Diagnostic Pathology, School of Basic Medical Sciences, Shandong Second Medical University, Weifang 261042, China"]["Department of Diagnostic Pathology, School of Basic Medical Sciences, Shandong Second Medical University, Weifang 261042, China","Department of Pathology, Affiliated Hospital of Shandong Second Medical University, Weifang 261041, China"]["Department of Diagnostic Pathology, School of Basic Medical Sciences, Shandong Second Medical University, Weifang 261042, China"]Uncoupling protein-2 (UCP2) controls the antioxidant response and redox homeostasis in cancer and is considered a potent molecular target for cancer treatment. However, the specific mechanism of UCP2 inhibition and its role in glioblastoma (GBM) have not yet been elucidated. Here, we attempt to identify a UCP2 inhibitor and study the underlying molecular mechanism in GBM. Bioinformatics analysis and immunohistochemistry are used to validate the high expression of UCP2 in GBM and its prognostic significance. Drug intervention and tumor xenograft experiments are conducted to determine the inhibitory effect of genipin, a UCP2 inhibitor, on UCP2. The mitochondrial membrane potential and key ferroptosis genes are examined to determine the occurrence of ferroptosis. High expression of UCP2 in GBM is associated with poor prognosis, and inhibiting UCP2 can alleviate the malignant behavior of GBM tumors. Genipin can downregulate the expression of GPX4 and upregulate the expression of ACSL4 by inhibiting UCP2, leading to ferroptosis and alleviating the malignant behavior of tumors. In summary, UCP2 is a potential therapeutic target for GBM. Genipin, which targets UCP2, effectively inhibits GBM development by inducing ferroptosis in vivo and in vitro. These findings indicate that genipin treatment based on UCP2 targeting has potential therapeutic applications with a clinical perspective for the treatment of GBM patients.https://www.sciengine.com/doi/10.3724/abbs.2024168genipinuncoupling protein-2ferroptosisglioblastomamalignant behavior of tumors |
| spellingShingle | Dong Hao Sun Kaixuan Wang Xuejie Cui Meimei Ma Yaping Li Kexin Duan Wanli Zhang Hongxing Zhang Liying Sheng Zhimei He Maotao Zhang Baogang Repurposed genipin targeting UCP2 exhibits antitumor activity through inducing ferroptosis in glioblastoma Acta Biochimica et Biophysica Sinica genipin uncoupling protein-2 ferroptosis glioblastoma malignant behavior of tumors |
| title | Repurposed genipin targeting UCP2 exhibits antitumor activity through inducing ferroptosis in glioblastoma |
| title_full | Repurposed genipin targeting UCP2 exhibits antitumor activity through inducing ferroptosis in glioblastoma |
| title_fullStr | Repurposed genipin targeting UCP2 exhibits antitumor activity through inducing ferroptosis in glioblastoma |
| title_full_unstemmed | Repurposed genipin targeting UCP2 exhibits antitumor activity through inducing ferroptosis in glioblastoma |
| title_short | Repurposed genipin targeting UCP2 exhibits antitumor activity through inducing ferroptosis in glioblastoma |
| title_sort | repurposed genipin targeting ucp2 exhibits antitumor activity through inducing ferroptosis in glioblastoma |
| topic | genipin uncoupling protein-2 ferroptosis glioblastoma malignant behavior of tumors |
| url | https://www.sciengine.com/doi/10.3724/abbs.2024168 |
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