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Marine Natural Product Chagosendine C Induces Cuproptosis in Colorectal Cancer Cells by Targeting FDX1

文献类型：期刊论文

作者Tao, Xiaoyu4,5,6; Wang, Hongru6; Wang, Qun6; Wang, Chengji3; Shao, Chang-Wei4; Jin, Yang4,5; Yu, Dianping6; Hu, Hongmei6; Zhang, Qing6; Xu, Mengting6
刊名JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
出版日期2025-10-15
卷号147期号:41页码:37089-37103
ISSN号0002-7863
DOI10.1021/jacs.5c07917
通讯作者Guo, Yue-Wei(ywguo@simm.ac.cn) ; Li, Xu-Wen(xwli@simm.ac.cn) ; Liu, Sanhong(liush@shutcm.edu.cn) ; Zhang, Weidong(wdzhangy@hotmail.com)
英文摘要Colorectal cancer (CRC) treatment is hampered by high recurrence rates and drug resistance. Cuproptosis, a copper-induced cell death mechanism, offers a new therapeutic approach. Here, we identified a marine natural product, chagosendine C (CHC), which kills tumor cells by increasing the intracellular copper ion concentration. CHC and related metal coordination homodimer alkaloids were rapidly synthesized and purified for further pharmacological study. In vitro, CHC significantly inhibited HCT116 and RKO CRC cell growth, induced G1 phase arrest and cell death, and overcame oxaliplatin resistance. In vivo, CHC suppressed colorectal tumor growth in mice at 40 mg/kg without obvious toxic effects. Mechanistically, CHC induces cuproptosis by targeting FDX1, increasing intracellular copper ions and ROS levels in tumor cells, and leading to cell death. Thus, CHC presents a novel CRC treatment strategy, showing strong antitumor activity and potential to overcome oxaliplatin resistance with promising clinical prospects.
WOS关键词METAL CHELATORS ; COPPER ; IONOPHORES ; DEATH
资助项目Key Technology Research and Development Program of Shandong Province[82141203] ; Key Technology Research and Development Program of Shandong Province[82374086] ; Key Technology Research and Development Program of Shandong Province[82104459] ; Key Technology Research and Development Program of Shandong Province[82022069] ; National Natural Science Foundation of China[2022YFC3502000] ; National Natural Science Foundation of China[2021YFF0502400] ; National Key Research and Development Program of China[ZD2021CY001] ; Shanghai Municipal Science and Technology Major Project[ZYYCXTDD-202004] ; Innovation Team and Talents Cultivation Program of the National Administration of Traditional Chinese Medicine[XDB1060000] ; Strategic Priority Research Program of the Chinese Academy of Sciences[2024CXPT028] ; Key R&D Program of Shandong Province[tsqn2023-12302] ; Taishan Scholars Program ; Key Marine Service Industry Program of Shandong Province[20YF1458700] ; Science and Technology Commission of Shanghai Municipality[2023YZZ02] ; Organizational Key Research and Development Program of Shanghai University of Traditional Chinese Medicine[2023-I2M-3-009] ; Organizational Key Research and Development Program of Shanghai University of Traditional Chinese Medicine[2060302-2305-02] ; CAMS Innovation Fund for Medical Sciences (CIFMS) ; Shanghai Advanced Research Institute, Chinese Academy of Sciences, China
WOS研究方向Chemistry
语种英语
WOS记录号WOS:001576224200001
出版者AMER CHEMICAL SOC
源URL[http://119.78.100.183/handle/2S10ELR8/321537]  
专题中国科学院上海药物研究所
通讯作者Guo, Yue-Wei; Li, Xu-Wen; Liu, Sanhong; Zhang, Weidong
作者单位1.Chinese Acad Med Sci & Peking Union Med Coll, Inst Med Plant Dev, Beijing 100193, Peoples R China
2.Second Mil Med Univ, Sch Pharm, Dept Phytochemistry, Shanghai 200433, Peoples R China
3.Shanghai Lab Anim Res Ctr, Shanghai 201203, Peoples R China
4.Bohai Rim Adv Res Inst Drug Discovery, Shandong Lab Yantai Drug Discovery, Yantai 264117, Peoples R China
5.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Chem Biol, Shanghai 201203, Peoples R China
6.Shanghai Univ Tradit Chinese Med, Shanghai Frontiers Sci Ctr TCM Chem Biol, Inst Interdisciplinary Integrat Med Res, State Key Lab Discovery & Utilizat Funct Component, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Tao, Xiaoyu,Wang, Hongru,Wang, Qun,et al. Marine Natural Product Chagosendine C Induces Cuproptosis in Colorectal Cancer Cells by Targeting FDX1[J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY,2025,147(41):37089-37103.
APA Tao, Xiaoyu.,Wang, Hongru.,Wang, Qun.,Wang, Chengji.,Shao, Chang-Wei.,...&Zhang, Weidong.(2025).Marine Natural Product Chagosendine C Induces Cuproptosis in Colorectal Cancer Cells by Targeting FDX1.JOURNAL OF THE AMERICAN CHEMICAL SOCIETY,147(41),37089-37103.
MLA Tao, Xiaoyu,et al."Marine Natural Product Chagosendine C Induces Cuproptosis in Colorectal Cancer Cells by Targeting FDX1".JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 147.41(2025):37089-37103.

入库方式： OAI收割

来源：上海药物研究所

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