Physalin B not only inhibits the ubiquitin-proteasome pathway but also induces incomplete autophagic response in human colon cancer cells in vitro

doi:10.1038/aps.2014.157

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 国家新药筛选中心

	Physalin B not only inhibits the ubiquitin-proteasome pathway but also induces incomplete autophagic response in human colon cancer cells in vitro
	Ma, Yi-ming; Han, Wei; Li, Jia; Hu, Li-hong; Zhou, Yu-bo
刊名	ACTA PHARMACOLOGICA SINICA
	2015-04
卷号	36 期号:4 页码:517-527
关键词	physalin B Physalis angulata L HCT116 colon cancer cells autophagy reactive oxygen species p38 mitogen-activated protein kinases microtubule-associated proteins apoptosis ubiquitins N-acetyl-L-cysteine
ISSN号	1671-4083
DOI	10.1038/aps.2014.157
文献子类	Article
英文摘要	Aim: To investigate the effects of physalin B insolated from Physalis divericata on human colon cancer cells in vitro and its anticancer mechanisms. Methods: Human HCT116 colon cancer cell line was tested. Cell viability and apoptosis were detected, and relevant proteins were measured using Western blot analyses. Autophagosomes were observed in stable GFP-LC3 HCT116 cells. Localization of autophagosomes and lysosomes was evaluated in GFP-LC3/RFP-LAMP1-co-transfected cells. Microtubules and F-actin microfilaments were observed with confocal microscope. Mitochondrial ROS (mito-ROS) was detected with flow cytometry in the cells stained with MitoSox dye. Results: Physalin B inhibited the viability of HCT116 cells with an IC50 value of 1.35 mu mol/L. Treatment of the cells with physalin B (2.5-10 mu mol/L) induced apoptosis and the cleavage of PARP and caspase-3. Meanwhile, physalin B treatment induced autophagosome formation, and accumulation of LC3-II and p62, but decreased Beclin 1 protein level. Marked changes of microtubules and F-actin microfilaments were observed in physalin B-treated cells, which led to the blockage of co-localization of autophagosomes and lysosomes. Physalin B treatment dose-dependently increased the phosphorylation of p38, ERK and JNK in the cells, whereas the p38 inhibitor SB202190, ERK inhibitor U0126 or JNK inhibitor SP600125 could partially reduce physalin B-induced PARP cleavage and p62 accumulation. Moreover, physalin B treatment dose-dependently increased mito-ROS production in the cells, whereas the ROS scavenger NAC could reverse physalin B-induced effects, including incomplete autophagic response, accumulation of ubiquitinated proteins, changes of microtubules and F-actin, activation of p38, ERK and JNK, as well as cell death and apoptosis. Conclusion: Physalin B induces mito-ROS, which not only inhibits the ubiquitin-proteasome pathway but also induces incomplete autophagic response in HCT116 cells in vitro.
资助项目	National Natural Science Foundation of China[81473244] ; National Natural Science Foundation of China[81270942] ; National Natural Science Foundation of China[81125023] ; National Science and Technology Major Projects for "Major New Drugs Innovation and Development"[2012ZX09301001-004] ; National Science and Technology Major Projects for "Major New Drugs Innovation and Development"[2013ZX09508104]
WOS关键词	ACTIVATED PROTEIN-KINASE ; BIOLOGICAL EVALUATION ; BECLIN 1 ; APOPTOSIS ; DIFFERENTIATION ; MACROAUTOPHAGY ; THERAPY ; ANALOGS ; STRESS ; DESIGN
WOS研究方向	Chemistry ; Pharmacology & Pharmacy
语种	英语
出版者	ACTA PHARMACOLOGICA SINICA
WOS记录号	WOS:000352203300012
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/276589]
专题	国家新药筛选中心上海中药现代化研究中心
通讯作者	Hu, Li-hong
作者单位	Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Ma, Yi-ming,Han, Wei,Li, Jia,et al. Physalin B not only inhibits the ubiquitin-proteasome pathway but also induces incomplete autophagic response in human colon cancer cells in vitro[J]. ACTA PHARMACOLOGICA SINICA,2015,36(4):517-527.
APA	Ma, Yi-ming,Han, Wei,Li, Jia,Hu, Li-hong,&Zhou, Yu-bo.(2015).Physalin B not only inhibits the ubiquitin-proteasome pathway but also induces incomplete autophagic response in human colon cancer cells in vitro.ACTA PHARMACOLOGICA SINICA,36(4),517-527.
MLA	Ma, Yi-ming,et al."Physalin B not only inhibits the ubiquitin-proteasome pathway but also induces incomplete autophagic response in human colon cancer cells in vitro".ACTA PHARMACOLOGICA SINICA 36.4(2015):517-527.