Da0324, an inhibitor of nuclear factor-kappa B activation, demonstrates selective antitumor activity on human gastric cancer cells

doi:10.2147/DDDT.S90081

科研成果详情

题名	Da0324, an inhibitor of nuclear factor-kappa B activation, demonstrates selective antitumor activity on human gastric cancer cells
作者	Jin, Rong1,3; Xia, Yiqun1,2; Chen, Qiuxiang1,2; Li, Wulan2,4; Chen, Dahui2; Ye, Hui2,5; Zhao, Chengguang2; Du, Xiaojing1,2; Shi, Dengjian 2; Wu, Jianzhang2; Liang, Guang2
发表日期	2016-12-31
发表期刊	DRUG DESIGN DEVELOPMENT AND THERAPY 影响因子和分区
语种	英语
原始文献类型	Article
关键词	gastric cancer anticancer drug NF-kappa B inhibitor asymmetric MACs apoptosis curcumin
其他关键词	ENDOPLASMIC-RETICULUM STRESS ; MONO-CARBONYL ANALOGS ; SIGNALING PATHWAY ; TRANSCRIPTION FACTOR ; INDUCED APOPTOSIS ; CARCINOMA-CELLS ; ALPHA KINASE ; P53 PATHWAY ; TNF-ALPHA ; CURCUMIN
摘要	Background: The transcription factor nuclear factor-kappa B (NF-kappa B) is constitutively activated in a variety of human cancers, including gastric cancer. NF-kappa B inhibitors that selectively kill cancer cells are urgently needed for cancer treatment. Curcumin is a potent inhibitor of NF-kappa B activation. Unfortunately, the therapeutic potential of curcumin is limited by its relatively low potency and poor cellular bioavailability. In this study, we presented a novel NF-kappa B inhibitor named Da0324, a synthetic asymmetric mono-carbonyl analog of curcumin. The purpose of this study is to research the expression of NF-kappa B in gastric cancer and the antitumor activity and mechanism of Da0324 on human gastric cancer cells. Methods: The expressions between gastric cancer tissues/cells and normal gastric tissues/cells of NF-kappa B were evaluated by Western blot. The inhibition viability of compounds on human gastric cancer cell lines SGC-7901, BGC-823, MGC-803, and normal gastric mucosa epithelial cell line GES-1 was assessed with the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay. Absorption spectrum method and high-performance liquid chromatography method detected the stability of the compound in vitro. The compound-induced changes of inducible NF-kappa B activation in the SGC-7901 and BGC-823 cells were examined by Western blot analysis and immunofluorescence methods. The antitumor activity of compound was performed by clonogenic assay, matrigel invasion assay, flow cytometric analysis, Western blot analysis, and Hoechst 33258 staining assay. Results: High levels of p65 were found in gastric cancer tissues and cells. Da0324 displayed higher growth inhibition against several types of gastric cancer cell lines and showed relatively low toxicity to GES-1. Moreover, Da0324 was more stable than curcumin in vitro. Western blot analysis and immunofluorescence methods showed that Da0324 blocked NF-kappa B activation. In addition, Da0324 significantly inhibited tumor proliferation and invasion, arrested the cell cycle, and induced apoptosis in vitro. Conclusion: The asymmetric mono-carbonyl analog of curcumin Da0324 exhibited significantly improved antigastric cancer activity. Da0324 may be a promising NF-kappa B/inhibitor for the selective targeting of cancer cells. However, further studies are needed in animals to validate these findings for the therapeutic use of Da0324.
资助项目	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81272462, 81202462, 81302642]; ZheJiang Province Natural Science Fund of China [LY14H160044]; Technology Foundation for Medical Science of Zhejiang Province [2012KYA129]
出版者	DOVE MEDICAL PRESS LTD
出版地	ALBANY
ISSN	1177-8881
卷号	10 页码:979-995
DOI	10.2147/DDDT.S90081
页数	17
WOS类目	Chemistry, Medicinal ; Pharmacology & Pharmacy
WOS研究方向	Pharmacology & Pharmacy
WOS记录号	WOS:000371168800001
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	27042000
PMC记录号	PMC4780725
SCOPUSEID	2-s2.0-84959497773
通讯作者地址	[Shi, Dengjian]Chemical Biology Research Center,School of Pharmaceutical Sciences,Wenzhou Medical University,Chashan, Wenzhou,325035,China
Scopus学科分类	Pharmacology;Pharmaceutical Science;Drug Discovery
引用统计	被引频次：23[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/15339
专题	附属第一医院基础医学院（机能实验教学中心）药学院（分析测试中心）第一临床医学院（信息与工程学院）、附属第一医院_计算机与信息管理系
通讯作者	Shi, Dengjian
作者单位	1.Department of Digestive Diseases,The First Affiliated Hospital of Wenzhou Medical University,China; 2.Chemical Biology Research Center,School of Pharmaceutical Sciences,Wenzhou Medical University,China; 3.Department of Epidemiology,The First Affiliated Hospital of Wenzhou Medical University,China; 4.College of Information Science and Computer Engineering,Wenzhou Medical College,China; 5.School of Basic Medical Sciences,Wenzhou Medical College,Wenzhou,China
第一作者单位	附属第一医院; 第一临床医学院（信息与工程学院）、附属第一医院
通讯作者单位	药学院（分析测试中心）; 生物有机与药物化学研究中心
第一作者的第一单位	附属第一医院
推荐引用方式 GB/T 7714	Jin, Rong,Xia, Yiqun,Chen, Qiuxiang,et al. Da0324, an inhibitor of nuclear factor-kappa B activation, demonstrates selective antitumor activity on human gastric cancer cells[J]. DRUG DESIGN DEVELOPMENT AND THERAPY,2016,10:979-995.
APA	Jin, Rong., Xia, Yiqun., Chen, Qiuxiang., Li, Wulan., Chen, Dahui., ... & Liang, Guang. (2016). Da0324, an inhibitor of nuclear factor-kappa B activation, demonstrates selective antitumor activity on human gastric cancer cells. DRUG DESIGN DEVELOPMENT AND THERAPY, 10, 979-995.
MLA	Jin, Rong,et al."Da0324, an inhibitor of nuclear factor-kappa B activation, demonstrates selective antitumor activity on human gastric cancer cells".DRUG DESIGN DEVELOPMENT AND THERAPY 10(2016):979-995.