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Sophflarine A, a novel matrine-derived alkaloid from Sophora flavescens with therapeutic potential for non-small cell lung cancer through ROS-mediated pyroptosis and autophagy

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资源类型：
Pubmed体系：
作者：
Luo Ding[1,2,3] * ; Dai Xiaoyong[4] * ; Tian He[1] * ; Fan Chunlin[2] ; Xie Huayan[1] ; Chen Nenghua[1] ; Wang Jinghao[1] ; Huang Laiqiang[4] ; Wang Hao[1] ; Wang Guocai[2] ; Zhang Yubo[2,3] ;
机构： [1]Department of Anesthesiology, The First Affifiliated Hospital of Jinan University, Guangzhou 510000, PR China [2]Institute of Traditional Chinese Medicine & Natural Products, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou 510632, PR China [3]Guangdong Clinical Translational Center for Targeted Drug, Department of Pharmacology, School of Medicine, Jinan University, Guangzhou 510632, PR China [4]Institute of Biopharmaceutical and Health Engineering, Shenzhen Key Laboratory of Gene and Antibody Therapy, State Key Laboratory of Chemical Oncogenomics, Shenzhen International Graduate School, Tsinghua University, Shenzhen, Guangdong 518055, PR China
出处：
DOI： 10.1016/j.phymed.2023.154909
ISSN：

关键词： Sophora flavescens Matrine-derived alkaloid Sophflarine a Non-small cell lung cancer Pyroptosis autophagy

摘要：
Novel compounds and more efficient treatment options are urgently needed for the treatment of non-small cell lung cancer (NSCLC). The decoction of Sophora flavescens has been used to treat NSCLC in the clinic, and matrine-type alkaloids are generally considered to be the key pharmacodynamic material basis. But the previous study showed that common matrine-type alkaloids exhibit significant cytotoxicity only when at concentrations close to the millimolar (mM) level. The key antitumor alkaloids in S. flavescens seem to have not yet been revealed.The aim of this study was to screen water-soluble matrine alkaloid with novel skeleton and enhanced activity from S. flavescens, and to reveal the pharmacological mechanism of its therapeutic effect on NSCLC.Alkaloid was obtained from S. flavescens by chromatographic separation methods. The structure of alkaloid was determined by spectroscopic methods, and single-crystal X-ray diffraction. The mechanism of anti-NSCLC in vitro with cellular models was evaluated by MTT assay, western blotting, cell migration and invasion assay, plate colony-formation assay, tube formation assay, immunohistochemistry assay, hematoxylin and eosin staining. The antitumor efficacy in vivo was test in NSCLC xenograft models.A novel water-soluble matrine-derived alkaloid incorporating 6/8/6/6 tetracyclic ring system, named sophflarine A (SFA), was isolated from the roots of S. flavescens. SFA had significantly enhanced cytotoxicity compared with the common matrine-type alkaloids, having an IC50 value of 11.3 μM in A549 and 11.5 μM in H820 cells at 48 h. Mechanistically, SFA promoted NSCLC cell death by inducing pyroptosis via activating the NLRP3/caspase-1/GSDMD signaling pathway, and inhibited cancer cell proliferation by increasing the ROS production to activate autophagy via blocking the PI3K/AKT/mTOR signaling pathway. Additionally, SFA also inhibited NSCLC cell migration and invasion by suppressing EMT pathway, and inhibited cancer cell colony formation and human umbilical vein endothelial cell angiogenesis. In concordance with the above results, SFA treatment blocked tumor growth in an A549 cell-bearing orthotopic mouse model.This study revealed a potential therapeutic mechanism of a novel matrine-derived alkaloid, which not only described a rational explanation for the clinical utilization of S. flavescens, but also provided a potential candidate compound for NSCLC treatment.Copyright © 2023 Elsevier GmbH. All rights reserved.

基金：
National Natural Science Foundation of China (nos. 82273803, 82074116), the Guangdong Basic and Applied Basic Research Foundation (no. 2020B1515020033, 2020A1515110453), Guangzhou Basic and Applied Basic Research Foundation (202102080022), Science and Technology Planning Project of Guangzhou City (no. 202201010485) and the high performance public computing service platform of Jinan University
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2022]版：
大类 | 1 区 医学
小类 | 1 区 药物化学 1 区 药学 1 区 全科医学与补充医学 1 区 植物科学
最新[2025]版：
大类 | 1 区 医学
小类 | 1 区 药物化学 1 区 全科医学与补充医学 1 区 药学 1 区 植物科学
第一作者：
第一作者机构： [1]Department of Anesthesiology, The First Affifiliated Hospital of Jinan University, Guangzhou 510000, PR China [2]Institute of Traditional Chinese Medicine & Natural Products, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou 510632, PR China [3]Guangdong Clinical Translational Center for Targeted Drug, Department of Pharmacology, School of Medicine, Jinan University, Guangzhou 510632, PR China
共同第一作者：
通讯作者：
通讯机构： [2]Institute of Traditional Chinese Medicine & Natural Products, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou 510632, PR China [3]Guangdong Clinical Translational Center for Targeted Drug, Department of Pharmacology, School of Medicine, Jinan University, Guangzhou 510632, PR China
推荐引用方式(GB/T 7714)：
Luo Ding,Dai Xiaoyong,Tian He,et al.Sophflarine A, a novel matrine-derived alkaloid from Sophora flavescens with therapeutic potential for non-small cell lung cancer through ROS-mediated pyroptosis and autophagy[J].Phytomedicine : international journal of phytotherapy and phytopharmacology.2023,116:154909.doi:10.1016/j.phymed.2023.154909.
APA：
Luo Ding,Dai Xiaoyong,Tian He,Fan Chunlin,Xie Huayan...&Zhang Yubo.(2023).Sophflarine A, a novel matrine-derived alkaloid from Sophora flavescens with therapeutic potential for non-small cell lung cancer through ROS-mediated pyroptosis and autophagy.Phytomedicine : international journal of phytotherapy and phytopharmacology,116,
MLA：
Luo Ding,et al."Sophflarine A, a novel matrine-derived alkaloid from Sophora flavescens with therapeutic potential for non-small cell lung cancer through ROS-mediated pyroptosis and autophagy".Phytomedicine : international journal of phytotherapy and phytopharmacology 116.(2023):154909

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