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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.
Yu, Jiaojiao; Zhang, Lijing; Peng, Jun; Ward, Richard; Hao, Peiqi; Wang, Jiwei; Zhang, Na; Yang, Yang; Guo, Xiaoxi; Xiang, Cheng; An, Su; Xu, Tian-Rui.
Afiliación
  • Yu J; Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China.
  • Zhang L; Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China.
  • Peng J; Department of Thoracic Surgery, the First People's Hospital of Yunnan Province, Kunming 650032, China; The Affiliated Hospital of Kunming University of Science and Technology, Kunming 650032, China.
  • Ward R; 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.
  • Hao P; Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China.
  • Wang J; Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China.
  • Zhang N; Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China.
  • Yang Y; Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China.
  • Guo X; Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China.
  • Xiang C; Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China.
  • An S; Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China; State Key Laboratory of Primate Biomedical Research, Kunming University of Science and Technology, Kunming 650500, China. Electronic address: aslxj@mail.ustc.edu.cn.
  • Xu TR; Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China; State Key Laboratory of Primate Biomedical Research, Kunming University of Science and Technology, Kunming 650500, China. Electronic address: tianruixu@kust.edu.cn.
Biochem Pharmacol ; 195: 114864, 2022 01.
Article en En | MEDLINE | ID: mdl-34861243
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fosfotransferasas / Quinolinas / Proteínas Proto-Oncogénicas c-met / Sistema de Señalización de MAP Quinasas / Proliferación Celular / Neoplasias Pulmonares Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans Idioma: En Revista: Biochem Pharmacol Año: 2022 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fosfotransferasas / Quinolinas / Proteínas Proto-Oncogénicas c-met / Sistema de Señalización de MAP Quinasas / Proliferación Celular / Neoplasias Pulmonares Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans Idioma: En Revista: Biochem Pharmacol Año: 2022 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido