Artemisinin synergizes with CCCP in autophagic cell death induction via ER stress in uveal melanoma
Summary: Uveal melanoma (UM) is the most common primary intraocular malignancy in adults, and it is associated with a poor prognosis due to the lack of effective targeted therapies. Artemisinin (ARS), a widely used antimalarial drug, has demonstrated anti-tumor effects in several types of cancer, in...
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Elsevier
2025-08-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004225012337 |
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| author | Minyue Xie Xiang Gu Zheng Zhao Yu Hua Qianru Wu Yizhen Tang Ai Zhuang Shengfang Ge Renbing Jia Jie Yu Jing Ruan Xianqun Fan |
| author_facet | Minyue Xie Xiang Gu Zheng Zhao Yu Hua Qianru Wu Yizhen Tang Ai Zhuang Shengfang Ge Renbing Jia Jie Yu Jing Ruan Xianqun Fan |
| author_sort | Minyue Xie |
| collection | DOAJ |
| description | Summary: Uveal melanoma (UM) is the most common primary intraocular malignancy in adults, and it is associated with a poor prognosis due to the lack of effective targeted therapies. Artemisinin (ARS), a widely used antimalarial drug, has demonstrated anti-tumor effects in several types of cancer, including UM. However, these effects are primarily observed at high concentrations, which restricts its broader use. Our study reveals mitochondrial uncoupler agents as synergistic partners with DHA in treating UM, both in vitro and in vivo. Specifically, the combination of DHA and CCCP, a representative mitochondrial uncoupler, induced endoplasmic reticulum (ER) stress by enhancing the binding of ATF4 and CHOP to the SESN2 promoter region. This ER stress subsequently activated autophagic cell death, augmenting UM cell eradication. Our findings suggest that combining DHA with mitochondrial protonophore uncouplers inhibits UM proliferation, underscoring the therapeutic promise of this approach for UM treatment. |
| format | Article |
| id | doaj-art-6975c7ed628a41299610dddb9b7c5a41 |
| institution | Kabale University |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-6975c7ed628a41299610dddb9b7c5a412025-08-20T03:29:10ZengElsevieriScience2589-00422025-08-0128811297210.1016/j.isci.2025.112972Artemisinin synergizes with CCCP in autophagic cell death induction via ER stress in uveal melanomaMinyue Xie0Xiang Gu1Zheng Zhao2Yu Hua3Qianru Wu4Yizhen Tang5Ai Zhuang6Shengfang Ge7Renbing Jia8Jie Yu9Jing Ruan10Xianqun Fan11Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, China; Department of Ophthalmology, Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, ChinaDepartment of Ophthalmology, Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, ChinaRenmin University of China, Beijing, ChinaDepartment of Ophthalmology, Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, ChinaBeijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, ChinaBeijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, ChinaDepartment of Ophthalmology, Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, ChinaDepartment of Ophthalmology, Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, ChinaDepartment of Ophthalmology, Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, ChinaDepartment of Ophthalmology, Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China; Corresponding authorDepartment of Ophthalmology, Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China; Corresponding authorDepartment of Ophthalmology, Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China; Corresponding authorSummary: Uveal melanoma (UM) is the most common primary intraocular malignancy in adults, and it is associated with a poor prognosis due to the lack of effective targeted therapies. Artemisinin (ARS), a widely used antimalarial drug, has demonstrated anti-tumor effects in several types of cancer, including UM. However, these effects are primarily observed at high concentrations, which restricts its broader use. Our study reveals mitochondrial uncoupler agents as synergistic partners with DHA in treating UM, both in vitro and in vivo. Specifically, the combination of DHA and CCCP, a representative mitochondrial uncoupler, induced endoplasmic reticulum (ER) stress by enhancing the binding of ATF4 and CHOP to the SESN2 promoter region. This ER stress subsequently activated autophagic cell death, augmenting UM cell eradication. Our findings suggest that combining DHA with mitochondrial protonophore uncouplers inhibits UM proliferation, underscoring the therapeutic promise of this approach for UM treatment.http://www.sciencedirect.com/science/article/pii/S2589004225012337BiochemistryCell biology |
| spellingShingle | Minyue Xie Xiang Gu Zheng Zhao Yu Hua Qianru Wu Yizhen Tang Ai Zhuang Shengfang Ge Renbing Jia Jie Yu Jing Ruan Xianqun Fan Artemisinin synergizes with CCCP in autophagic cell death induction via ER stress in uveal melanoma iScience Biochemistry Cell biology |
| title | Artemisinin synergizes with CCCP in autophagic cell death induction via ER stress in uveal melanoma |
| title_full | Artemisinin synergizes with CCCP in autophagic cell death induction via ER stress in uveal melanoma |
| title_fullStr | Artemisinin synergizes with CCCP in autophagic cell death induction via ER stress in uveal melanoma |
| title_full_unstemmed | Artemisinin synergizes with CCCP in autophagic cell death induction via ER stress in uveal melanoma |
| title_short | Artemisinin synergizes with CCCP in autophagic cell death induction via ER stress in uveal melanoma |
| title_sort | artemisinin synergizes with cccp in autophagic cell death induction via er stress in uveal melanoma |
| topic | Biochemistry Cell biology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004225012337 |
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