Oligomannurarate sulfate blocks tumor growth by inhibiting NF-kappa B activation

doi:10.1038/aps.2010.13

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药理学第一研究室

	Oligomannurarate sulfate blocks tumor growth by inhibiting NF-kappa B activation
	Zhang, Jing; Chen, Yi; Xin, Xian-liang; Li, Qiu-ning; Li, Ming; Lin, Li-ping; Geng, Mei-yu; Ding, Jian
刊名	ACTA PHARMACOLOGICA SINICA
	2010-03
卷号	31 期号:3 页码:375-381
关键词	oligosaccharide sulfate NF-kappa B inhibitors tumor growth heparanase liver neoplasm breast neoplasm
ISSN号	1671-4083
DOI	10.1038/aps.2010.13
文献子类	Article
英文摘要	Aim: JG3, a novel marine-derived oligosaccharide, significantly inhibits angiogenesis and tumor metastasis by blocking heparanase activity. It also arrests tumor growth, an effect that is not fully explained by its anti-heparanase activity. Here we sought to identify the mechanisms underlying JG3-mediated inhibition of tumor growth. Methods: Heparanase expression was assessed by RT-PCR and Western blotting. NF-kappa B activation status was determined using immunofluorescence, Western blotting, DNA-binding and transcription-activity assays. The effect of JG3 on upstream components of the NF-kappa B pathway and on selected transcription factors were monitored by Western blotting. The antitumor effect of JG3 and its relation to NF-kappa B activation were evaluated using four different tumor xenograft models. Results: We found that JG3 effectively inhibited NF-kappa B activation independent of heparanase expression. Our results indicate that JG3 inactivated NF-kappa B by interfering with the activation of upstream components of the NF-kappa B pathway without generally affecting the nuclear translocation of transcription factors. Further, in vivo studies demonstrated that JG3 effectively arrested the growth of tumors derived from cell lines in which NF-kappa B was constitutively active (BEL-7402 liver carcinoma and MDA-MB-435s breast carcinoma), but did not affect the growth of tumors derived from NF-kappa B-negative cell lines (SGC-7901 gastric cancer and HO-8910 ovarian carcinoma). Conclusion: Our data indicate that NF-kappa B mediates the JG3-induced arrest of tumor growth. These results define a new mechanism of action of JG3 and highlight the potential for JG3 as a promising lead molecule in cancer therapy.
资助项目	Natural Science Foundation of China for Distinguished Young Scholars[30725046] ; National Basic Research Program Grant of China[2003CB716400] ; Natural Science Foundation of China for Innovation Research Group[30721005] ; Chinese Academy of Sciences[KSCX2-YWR-25] ; Key New Drug Creation and Manufacturing Program[2009ZX09103-073] ; 863 Hi-Tech Program of China[2006AA020602]
WOS关键词	CANCER METASTASIS ; HEPARANASE ; ANGIOGENESIS ; PROGRESSION ; EXPRESSION ; RESISTANCE ; CARCINOMA ; PATHWAYS ; THERAPY ; CELLS
WOS研究方向	Chemistry ; Pharmacology & Pharmacy
语种	英语
CSCD记录号	CSCD:3893559
出版者	ACTA PHARMACOLOGICA SINICA
WOS记录号	WOS:000275824400014
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/278952]
专题	药理学第一研究室中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Geng, Mei-yu
作者单位	Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Div Antitumor Pharmacol, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Zhang, Jing,Chen, Yi,Xin, Xian-liang,et al. Oligomannurarate sulfate blocks tumor growth by inhibiting NF-kappa B activation[J]. ACTA PHARMACOLOGICA SINICA,2010,31(3):375-381.
APA	Zhang, Jing.,Chen, Yi.,Xin, Xian-liang.,Li, Qiu-ning.,Li, Ming.,...&Ding, Jian.(2010).Oligomannurarate sulfate blocks tumor growth by inhibiting NF-kappa B activation.ACTA PHARMACOLOGICA SINICA,31(3),375-381.
MLA	Zhang, Jing,et al."Oligomannurarate sulfate blocks tumor growth by inhibiting NF-kappa B activation".ACTA PHARMACOLOGICA SINICA 31.3(2010):375-381.