Mechanistic insights on cytotoxicity of KOLR, Cinnamomum pauciflorum Nees leaf derived active ingredient, by targeting signaling complexes of phosphodiesterase 3B and rap guanine nucleotide exchange factor 3
机构：[1]Tongde Hosp Zhejiang Prov, Zhejiang Acad Tradit Chinese Med, Canc Inst Integrated Tradit Chinese & Western Med, Hangzhou 310012, Zhejiang, Peoples R China[2]Sichuan Normal Univ, Coll Life Sci, Chengdu 610101, Sichuan, Peoples R China[3]Guangzhou Univ Chinese Med, Guangdong Prov Hosp Tradit Chinese Med, Clin Med Coll 2, Guang Zhou, Guangdong, Peoples R China广东省中医院[4]Peoples Liberat Army Joint Logist Support Force 9, Nursing Dept, Hangzhou, Zhejiang, Peoples R China[5]Yibin Univ, Key Lab Fermentat Resources & Applicat Univ Sichu, Yibin, Sichuan, Peoples R China
Protein signaling complexes play important roles in prevention of several cancer types and can be used for development of targeted therapy. The roles of signaling complexes of phosphodiesterase 3B (PDE3B) and Rap guanine nucleotide exchange factor 3 (RAPGEF3), which are two important enzymes of cyclic adenosine monophosphate (cAMP) metabolism, in cancer have not been fully explored. In the current study, a natural product Kaempferol-3-O-(3 '',4 ''-di-E-p-coumaroyl)-alpha-L-rhamnopyranoside designated as KOLR was extracted from Cinnamomum pauciflorum Nees leaves. KOLR exhibited higher cytotoxic effects against BxCP-3 pancreatic cancer cell line. In BxPC-3 cells, the KOLR could enhance the formation of RAPGEF 3/ PDE3B protein complex to inhibit the activation of Rap-1 and PI3K-AKT pathway, thereby promoting cell apoptosis and inhibiting cell metastasis. Mutation of RAPGEF3 G557A or low expression of PDE3B inactivated the binding action of KOLR resulting in KOLR resistance. The findings of this study show that PDE3B/RAPGEF3 complex is a potential therapeutic cancer target.
基金：
National Natural Science Foundation of China,
Grant/Award Numbers: 82074093, 81673809,
81673781; Natural Science Foundation of
Zhejiang Province, Grant/Award Number:
LY19H280005; Open Project of Provincial Key
Laboratory, Grant/Award Number:
2018XLZ012; The Scientific and Technological
Program of Sichuan province, Grant/Award
Number: 20YYJC4341; Zhejiang Traditional
Chinese Medicine Administration, Grant/
Award Numbers: 2020ZX003, 2021AX002,
2016ZQ002
第一作者机构：[1]Tongde Hosp Zhejiang Prov, Zhejiang Acad Tradit Chinese Med, Canc Inst Integrated Tradit Chinese & Western Med, Hangzhou 310012, Zhejiang, Peoples R China
共同第一作者：
通讯作者：
通讯机构：[1]Tongde Hosp Zhejiang Prov, Zhejiang Acad Tradit Chinese Med, Canc Inst Integrated Tradit Chinese & Western Med, Hangzhou 310012, Zhejiang, Peoples R China[2]Sichuan Normal Univ, Coll Life Sci, Chengdu 610101, Sichuan, Peoples R China[*1]Cancer Institute of Integrated tradition Chinese and Western Medicine, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang 310012, China.[*2]College of Life Science, Sichuan Normal University, Chengdu, Sichuan, 610101, China.
推荐引用方式(GB/T 7714)：
Li Mingqian,Li Fei,Chen Jiabin,et al.Mechanistic insights on cytotoxicity of KOLR, Cinnamomum pauciflorum Nees leaf derived active ingredient, by targeting signaling complexes of phosphodiesterase 3B and rap guanine nucleotide exchange factor 3[J].PHYTOTHERAPY RESEARCH.2022,36(9):3540-3554.doi:10.1002/ptr.7521.
APA：
Li, Mingqian,Li, Fei,Chen, Jiabin,Su, He,Chen, Guanping...&Chai, Kequn.(2022).Mechanistic insights on cytotoxicity of KOLR, Cinnamomum pauciflorum Nees leaf derived active ingredient, by targeting signaling complexes of phosphodiesterase 3B and rap guanine nucleotide exchange factor 3.PHYTOTHERAPY RESEARCH,36,(9)
MLA：
Li, Mingqian,et al."Mechanistic insights on cytotoxicity of KOLR, Cinnamomum pauciflorum Nees leaf derived active ingredient, by targeting signaling complexes of phosphodiesterase 3B and rap guanine nucleotide exchange factor 3".PHYTOTHERAPY RESEARCH 36..9(2022):3540-3554
