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A dual-target pectin-like polysaccharide LRP01B from Lamiophlomis rotata induces pancreatic cancer cell apoptosis in vitro and in vivo by causing mitochondrial dysfunction

文献类型：期刊论文

作者Xie, Jianhao1,2; Su, Juan1; Zhou, Wanqi1,4,5; Cai, Simin1; Liao, Wenfeng1; Zong, Jianing1,7; Peng, Junfeng1,6; Qu, Huanhuan1; He, Fei1; Ding, Kan1,2,3,5,7,8
刊名INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
出版日期2025-10-01
卷号327页码:17
关键词Pancreatic cancer Pectin-like polysaccharide Mitochondria
ISSN号0141-8130
DOI10.1016/j.ijbiomac.2025.147227
英文摘要Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant cancer with limited treatment options. Recent pharmacological studies suggested that Lamiophlomis rotata might contain components with antitumor activities. In this study, we aimed to investigate the potential of polysaccharides as active components in Lamiophlomis rotata. Our findings suggest that a polysaccharide, LRP01B, from Lamiophlomis rotata induces PDAC cells apoptosis by causing mitochondrial dysfunction and oxidative stress in vitro and in vivo. LRP01B is a homogeneous polysaccharide with a molecular weight of 15.9 kDa, composed of galactose, glucose, xylose, arabinose, rhamnose, and galacturonic acid in a molar ratio of 0.7: 0.3: 0.1: 1.1: 1.0: 4.3. The backbone of LRP01B mainly consists of 1,4-linked alpha-GalpA, 1,2-linked alpha-Rhap, and 1,3-linked alpha-GalpA, with existence of arabinose and xylose on the side chain. In vivo experiments demonstrate that LRP01B significantly inhibits pancreatic tumor growth in a patient-derived xenograft nude mouse model. Mechanism studies uncover that LRP01B induces apoptosis of PDAC cells through mitochondrial dysfunction and oxidative stress by recruiting TNF-related apoptosis-inducing ligand (TRAIL) to TRAIL-R1, which leads to the binding of LRP01B to both TRAIL and TRAIL-R1. Our results demonstrate that LRP01B is a dual-targeting polysaccharide with anti-PDAC activity and may be a promising anti-PDAC drug candidate.
WOS关键词GALECTIN-3 INHIBITOR ; ELUCIDATION ; HOMEOSTASIS
资助项目Shanghai Municipal Science and Technology Major Project ; National Natural Science Foundation of China[32271332] ; National Natural Science Foundation of China[31870801] ; National Natural Science Foundation of China[82404940] ; Lingang Laboratory[LG202101-01-02] ; Zhongshan Municipal Bureau of Science and Technology ; High-level new R D institute[2019B090904008] ; High-level Innovative Research Institute from Department of Science and Technology of Guangdong Province[2021B0909050003] ; Yangfan Project of Shanghai Science and Technology Commission[20YF1457300]
WOS研究方向Biochemistry & Molecular Biology ; Chemistry ; Polymer Science
语种英语
WOS记录号WOS:001568792100007
出版者ELSEVIER
源URL[http://119.78.100.183/handle/2S10ELR8/321459]  
专题国家级研究中心_原创新药研究全国重点实验室
通讯作者He, Fei; Ding, Kan
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, Carbohydrate Drug Res Ctr, CAS Key Lab Receptor Res,State Key Lab Drug Res, Shanghai 201203, Peoples R China
2.Univ Chinese Acad Sci, 19 A Yuquan Rd, Beijing 100049, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Mat Med, Zhongshan Inst Drug Discovery, SSIP Healthcare & Med Demonstrat Zone, Zhongshan 528400, Guangdong, Peoples R China
4.ShanghaiTech Univ, Sch Phys Sci & Technol, Shanghai 201210, Peoples R China
5.Lingang Lab, Shanghai, Peoples R China
6.Naval Med Univ, Affiliated Hosp 2, Dept Pancreat Biliary Surg, Shanghai Changzheng Hosp, 415 Fengyang Rd, Shanghai 200003, Peoples R China
7.Nanjing Univ Chinese Med, Sch Chinese Mat Med, 138 Xianlin Ave, Nanjing 210029, Jiangsu, Peoples R China
8.Henan Univ Chinese Med, Henan Polysaccharide Res Ctr, Zhengzhou, Peoples R China
推荐引用方式
GB/T 7714		 Xie, Jianhao,Su, Juan,Zhou, Wanqi,et al. A dual-target pectin-like polysaccharide LRP01B from Lamiophlomis rotata induces pancreatic cancer cell apoptosis in vitro and in vivo by causing mitochondrial dysfunction[J]. INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES,2025,327:17.
APA Xie, Jianhao.,Su, Juan.,Zhou, Wanqi.,Cai, Simin.,Liao, Wenfeng.,...&Ding, Kan.(2025).A dual-target pectin-like polysaccharide LRP01B from Lamiophlomis rotata induces pancreatic cancer cell apoptosis in vitro and in vivo by causing mitochondrial dysfunction.INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES,327,17.
MLA Xie, Jianhao,et al."A dual-target pectin-like polysaccharide LRP01B from Lamiophlomis rotata induces pancreatic cancer cell apoptosis in vitro and in vivo by causing mitochondrial dysfunction".INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES 327(2025):17.

入库方式： OAI收割

来源：上海药物研究所

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