Discovery of a novel protein kinase C activator from Croton tiglium for inhibition of non-small cell lung cancer

doi:10.1016/j.phymed.2019.153100

	Discovery of a novel protein kinase C activator from Croton tiglium for inhibition of non-small cell lung cancer
	Wang Yuwei 2; Tang Chunping 5; Yao Sheng 5; Lai Huanling 2; Li Runze 2; Xu Jiahui 2; Wang Qianqian 2; Fan Xing Xing 2; Wu Qi Biao 2; Lai-Han, Leung Elaine 1,2,3,4
刊名	PHYTOMEDICINE
	2019-12-01
卷号	65 页码:11
关键词	Non-small cell lung cancer Natural product Croton tiglium Protein kinase C Molecular modelling
ISSN号	0944-7113
DOI	10.1016/j.phymed.2019.153100
通讯作者	Lai-Han, Leung Elaine(lhleung@must.edu.mo) ; Ye Yang(yye@mail.shcnc.ac.cn) ; Yao Xiaojun(xjyao@must.edu.mo)
英文摘要	Background: The incidence of non-small cell lung cancer (NSCLC) accounts for approximately 85-90% of lung cancer, which has been shown to be challenging for treatment owing to poorly understanding of pathological mechanisms. Natural products serve as a source of almost all pharmaceutical preparations or offer guidance for those chemicals that have entered clinical trials, especially in NSCLC. Purpose: We investigated the effect of B10G5, a natural products isolated from the Croton tiglium, in human nonsmall cell lung canceras as a protein kinase C (PKC) activator. Methods: The cell viability assay was evaluated by the MTT assay. The apoptosis and cell cycle distribution were assessed by flow cytometry. Reactive oxygen species (ROS) production was determined by using the fluorescent probe DCFDA. Cell migration ability of H1975 cells was analyzed by using the wound healing assay. The inhibiting effect of B10G5 against the phosphorylation level of the substrate by PKCs was assessed by using homogeneous time-resolved fluorescence (HTRF) technology. The correlation between PKCs and overall survival (OS) of Lung Adenocarcinoma (LUAD) patients was analysis by TCGA portal. The binding mode between B10GS and the PKC isoforms was explored by molecular docking. Protein expression was detected by western blotting analysis. Results: B10G5 suppressed cell proliferation and colony formation, as well as migration ability of NSCLC cells, without significant toxic effect on normal lung cells. B10G5 induced the cell apoptosis through the development of PARP cleavage, which is evidenced by means of the production of mitochondrial ROS. In addition, the B10G5 inhibitory effect was also related to the cell cycle arrest at G2/M phase. Mechanistically, molecular modelling technology suggested that the potential target of B10G5 was associated with PKC family. In vitro PKC kinase assay indicated that B10G5 effectively activated the PKC activity. Western blotting data revealed that B10G5 upregulated PKC to activate PKC-mediated RAF/MEK/ERK pathway. Conclusion: Our results showed that B10G5, a naturally occurring phorbol ester, considered to be a potential and a valuable therapeutic chemical in the treatment of NSCLC.
资助项目	Macao Science and Technology Development Fund[0003/2018/A1] ; Macao Science and Technology Development Fund[0096/2018/A3] ; Macao Science and Technology Development Fund[130/2017/A3] ; Macao Science and Technology Development Fund[082/2013/A3] ; Macao Science and Technology Development Fund[082/2015/A3] ; Macao Science and Technology Development Fund[046/2016/A2] ; Macao Science and Technology Development Fund[010/2016/A1]
WOS关键词	DELTA ; PREDICTION ; CARCINOMA ; APOPTOSIS ; EPSILON ; REVEAL ; GROWTH ; DOMAIN ; MODEL ; IOTA
WOS研究方向	Plant Sciences ; Pharmacology & Pharmacy ; Integrative & Complementary Medicine
语种	英语
出版者	ELSEVIER GMBH
WOS记录号	WOS:000500561700011
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/282005]
专题	中国科学院上海药物研究所
通讯作者	Lai-Han, Leung Elaine; Ye Yang; Yao Xiaojun
作者单位	1.Guangzhou Med Univ, Guangzhou Inst Resp Hlth, Dept Thorac Surg, Affiliated Hosp 1, Guangzhou, Guangdong, Peoples R China 2.Macau Univ Sci & Technol, State Key Lab Qual Res Chinese Med, Ave Wai Long, Taipa, Macao, Peoples R China 3.Hubei Univ Med, Taihe Hosp, Resp Med Dept, Shiyan, Hubei, Peoples R China 4.Guangzhou Med Univ, State Key Lab Resp Dis, Affiliated Hosp 1, Guangzhou, Guangdong, Peoples R China 5.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai, Peoples R China
推荐引用方式 GB/T 7714	Wang Yuwei,Tang Chunping,Yao Sheng,et al. Discovery of a novel protein kinase C activator from Croton tiglium for inhibition of non-small cell lung cancer[J]. PHYTOMEDICINE,2019,65:11.
APA	Wang Yuwei.,Tang Chunping.,Yao Sheng.,Lai Huanling.,Li Runze.,...&Yao Xiaojun.(2019).Discovery of a novel protein kinase C activator from Croton tiglium for inhibition of non-small cell lung cancer.PHYTOMEDICINE,65,11.
MLA	Wang Yuwei,et al."Discovery of a novel protein kinase C activator from Croton tiglium for inhibition of non-small cell lung cancer".PHYTOMEDICINE 65(2019):11.