2-Methoxystypandrone inhibits signal transducer and activator of transcription 3 and nuclear factor-jB signaling by inhibiting Janus kinase 2 and IjB kinase

doi:10.1111/cas.12359

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

	2-Methoxystypandrone inhibits signal transducer and activator of transcription 3 and nuclear factor-jB signaling by inhibiting Janus kinase 2 and IjB kinase
	Kuang, Shan 2; Qi, Chunting 2; Liu, Jiawei 1; Sun, Xiaoxiao 2; Zhang, Qing2 ; Sima, Zhenhua 1; Liu, Jingli 2; Li, Wuguo 1; Yu, Qiang2
刊名	CANCER SCIENCE
	2014-04
卷号	105 期号:4 页码:473-480
关键词	2-Methoxystypandrone anticancer drug Janus kinase 2 signal transducer and activator of transcription 3 pathway natural compound tumor necrosis factor- nuclear factor-B pathway
ISSN号	1347-9032
DOI	10.1111/cas.12359
文献子类	Article
英文摘要	Constitutive activation of the signal transducer and activator of transcription 3 (STAT3) or the nuclear factor-B (NF-B) pathway occurs frequently in cancer cells and contributes to oncogenesis. The activation of Janus kinase 2 (JAK2) and IB kinase (IKK) are key events in STAT3 and NF-B signaling, respectively. We have identified 2-methoxystypandrone (2-MS) from a traditional Chinese medicinal herb Polygonumcuspidatum as a novel dual inhibitor of JAK2 and IKK. 2-MS inhibits both interleukin-6-induced and constitutively-activated STAT3, as well as tumor necrosis factor--induced NF-B activation. 2-MS specifically inhibits JAK and IKK kinase activities but has little effect on activities of other kinases tested. The inhibitory effects of 2-MS on STAT3 and NF-B signaling can be eliminated by DTT or glutathione and can last for 4h after a pulse treatment. Furthermore, 2-MS inhibits growth and induces death of tumor cells, particularly those with constitutively-activated STAT3 or NF-B signaling. We propose that the natural compound 2-MS, as a potent dual inhibitor of STAT3 and NF-B pathways, is a promising anticancer drug candidate. Natural compound from Polygonum cuspidatum as a promising anticancer drug candidate by inhibiting STAT3 and NF-B signalling. A novel dual kinase inhibitor of JAK2 and IKK. May form adducts with the thiols of the cysteins in the JAK2 and IKK proteins.
资助项目	China Ministry of Science and Technology[2013ZX09102015] ; China Ministry of Science and Technology[2013ZX10002010-009] ; China National Natural Science Foundation[81373432] ; China National Natural Science Foundation[31129004] ; China National Natural Science Foundation[91129701] ; China National Natural Science Foundation[91213304] ; National Science and Technology 973[2012CB910704] ; National Science and Technology 973[2013CB910900]
WOS关键词	FACTOR-KAPPA-B ; POLYGONUM-CUSPIDATUM ; STAT3 ACTIVATION ; CANCER-CELLS ; IN-VIVO ; CONSTITUTIVE ACTIVATION ; ALPHA KINASE ; TUMOR-GROWTH ; PATHWAY ; APOPTOSIS
WOS研究方向	Oncology
语种	英语
出版者	WILEY-BLACKWELL
WOS记录号	WOS:000334238800014
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/277136]
专题	药理学第一研究室
通讯作者	Yu, Qiang
作者单位	1.Guangzhou Univ Chinese Med, Minist Educ, Key Lab Chinese Med Plants Resource Lingnan, Res Ctr Med Plants Resource Sci & Engn, Guangzhou, Guangdong, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Div Tumor Pharmacol, Shanghai 200031, Peoples R China;
推荐引用方式 GB/T 7714	Kuang, Shan,Qi, Chunting,Liu, Jiawei,et al. 2-Methoxystypandrone inhibits signal transducer and activator of transcription 3 and nuclear factor-jB signaling by inhibiting Janus kinase 2 and IjB kinase[J]. CANCER SCIENCE,2014,105(4):473-480.
APA	Kuang, Shan.,Qi, Chunting.,Liu, Jiawei.,Sun, Xiaoxiao.,Zhang, Qing.,...&Yu, Qiang.(2014).2-Methoxystypandrone inhibits signal transducer and activator of transcription 3 and nuclear factor-jB signaling by inhibiting Janus kinase 2 and IjB kinase.CANCER SCIENCE,105(4),473-480.
MLA	Kuang, Shan,et al."2-Methoxystypandrone inhibits signal transducer and activator of transcription 3 and nuclear factor-jB signaling by inhibiting Janus kinase 2 and IjB kinase".CANCER SCIENCE 105.4(2014):473-480.