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Dictamnine, a novel c-Met inhibitor, suppresses the proliferation of lung cancer cells by downregulating the PI3K/AKT/mTOR and MAPK signaling pathways.

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收录情况： ◇ SCIE

作者：
Yu Jiaojiao[1] * ; Zhang Lijing[1] * ; Peng Jun[3,4] ; Ward Richard[5] ; Hao Peiqi[1] ; Wang Jiwei[1] ; Zhang Na[1] ; Yang Yang[1] ; Guo Xiaoxi[1] ; Xiang Cheng[1] ; An Su[1,2,*1] ; Xu Tian-Rui[1,2,*1] ;
机构： [1]Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China [2]State Key Laboratory of Primate Biomedical Research, Kunming University of Science and Technology, Kunming 650500, China [3]Department of Thoracic Surgery, the First People’s Hospital of Yunnan Province, Kunming 650032, China [4]The Affiliated Hospital of Kunming University of Science and Technology, Kunming 650032, China [5]Centre for Translational Pharmacology, Institute of Molecular Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK
出处：
DOI： 10.1016/j.bcp.2021.114864
ISSN：

关键词： Dictamnine c-Met Lung adenocarcinoma PI3K/AKT/mTOR MAPK Gefitinib resistance

摘要：
Dictamnine (Dic), a naturally occurring small-molecule furoquinoline alkaloid isolated from the root bark of Dictamnus dasycarpus Turcz., is reported to display anticancer properties. However, little is known about the direct target proteins and anticancer mechanisms of Dic. In the current study, Dic was found to suppress the growth of lung cancer cells in vitro and in vivo, and to attenuate the activation of PI3K/AKT/mTOR and mitogen-activated protein kinase (MAPK) signaling pathways by inhibiting the phosphorylation and activation of receptor tyrosine kinase c-Met. Moreover, the binding of Dic to c-Met was confirmed by using cellular thermal shift assay (CETSA) and drug affinity responsive target stability (DARTS) assay. Among all cancer cell lines tested, Dic inhibited the proliferation of c-Met-dependent EBC-1 cells with the greatest potency (IC50 = 2.811 μM). Notably, Dic was shown to synergistically improve the chemo-sensitivity of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI)-resistant lung cancer cells to gefitinib and osimertinib. These results suggest that Dic is a c-Met inhibitor that can serve as a potential therapeutic agent in the treatment of lung cancer, especially against EGFR TKI-resistant and c-Met-dependent lung cancer.Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

基金：
National Natural Science Foundation of China (NSFC) (grant number 81760264, 81960394 and 81960659), the Key Fund of Yunnan Basic Research Program (grant number 202001AS070024), the National Key Research and Development Project (grant number 2018YFA0801404) and conducted in the University Based Provincial Key Laboratory of Screening and Utilization of Targeted Drugs.
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外文
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中科院(CAS)分区：
出版当年[2022]版：
大类 | 2 区 医学
小类 | 2 区 药学
最新[2025]版：
大类 | 2 区 医学
小类 | 2 区 药学
JCR分区：
出版当年[2021]版：
Q1 PHARMACOLOGY & PHARMACY
最新[2023]版：
Q1 PHARMACOLOGY & PHARMACY

影响因子： 最新[2023版] 最新五年平均 出版当年[2021版] 出版当年五年平均 出版前一年[2020版] 出版后一年[2022版]

第一作者：
第一作者机构： [1]Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China
共同第一作者：
通讯作者：
通讯机构： [1]Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China [2]State Key Laboratory of Primate Biomedical Research, Kunming University of Science and Technology, Kunming 650500, China [*1]Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China
推荐引用方式(GB/T 7714)：
Yu Jiaojiao,Zhang Lijing,Peng Jun,et al.Dictamnine, a novel c-Met inhibitor, suppresses the proliferation of lung cancer cells by downregulating the PI3K/AKT/mTOR and MAPK signaling pathways.[J].BIOCHEMICAL PHARMACOLOGY.2022,195:doi:10.1016/j.bcp.2021.114864.
APA：
Yu Jiaojiao,Zhang Lijing,Peng Jun,Ward Richard,Hao Peiqi...&Xu Tian-Rui.(2022).Dictamnine, a novel c-Met inhibitor, suppresses the proliferation of lung cancer cells by downregulating the PI3K/AKT/mTOR and MAPK signaling pathways..BIOCHEMICAL PHARMACOLOGY,195,
MLA：
Yu Jiaojiao,et al."Dictamnine, a novel c-Met inhibitor, suppresses the proliferation of lung cancer cells by downregulating the PI3K/AKT/mTOR and MAPK signaling pathways.".BIOCHEMICAL PHARMACOLOGY 195.(2022)

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