(5R)-5-hydroxytriptolide (LLDT-8), a novel immunosuppressant in clinical trials, exhibits potent antitumor activity via transcription inhibition

doi:10.1016/j.canlet.2012.05.004

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	(5R)-5-hydroxytriptolide (LLDT-8), a novel immunosuppressant in clinical trials, exhibits potent antitumor activity via transcription inhibition
	Wang, Lei; Xu, Yongping; Fu, Li; Li, Yuanchao; Lou, Liguang
刊名	CANCER LETTERS
	2012-11-01
卷号	324 期号:1 页码:75-82
关键词	(5R)-5-hydroxytriptolide Triptolide Transcription inhibition
ISSN号	0304-3835
DOI	10.1016/j.canlet.2012.05.004
文献子类	Article
英文摘要	(5R)-5-hydroxytriptolide (LLDT-8), a triptolide derivative, is a low-toxicity immunosuppressant in Phase I clinical trials. Here, we demonstrate that LLDT-8 displays broad-spectrum, potent (nanomolar level IC(50)s) antitumor activity, and induces S-phase cell-cycle arrest and apoptosis in vitro. Notably. LLDT-8 effectively overcomes multidrug resistance mediated by P-glycoprotein. In vivo, LLDT-8 demonstrates potent antitumor activity, particularly against human ovarian cancer 3AO and prostate cancer PC-3 xenografts in nude mice. The antitumor activity of LLDT-8 is achieved by virtue of its general inhibition of gene transcription. Our results indicate that LLDT-8 is a novel transcription inhibitor with potential for cancer therapy, particularly for cancers with drug resistance mediated by P-glycoprotein. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
资助项目	National Natural Science Foundation of China[90813009]
WOS关键词	MEDIATED DRUG-RESISTANCE ; RNA-POLYMERASE-II ; ALLOGRAFT-REJECTION ; INDUCED APOPTOSIS ; CANCER-THERAPY ; ACTINOMYCIN-D ; CELL-CYCLE ; TRIPTOLIDE ; AGENT ; RATS
WOS研究方向	Oncology
语种	英语
出版者	ELSEVIER IRELAND LTD
WOS记录号	WOS:000307420200008
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/277900]
专题	药理学第一研究室
通讯作者	Lou, Liguang
作者单位	Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Wang, Lei,Xu, Yongping,Fu, Li,et al. (5R)-5-hydroxytriptolide (LLDT-8), a novel immunosuppressant in clinical trials, exhibits potent antitumor activity via transcription inhibition[J]. CANCER LETTERS,2012,324(1):75-82.
APA	Wang, Lei,Xu, Yongping,Fu, Li,Li, Yuanchao,&Lou, Liguang.(2012).(5R)-5-hydroxytriptolide (LLDT-8), a novel immunosuppressant in clinical trials, exhibits potent antitumor activity via transcription inhibition.CANCER LETTERS,324(1),75-82.
MLA	Wang, Lei,et al."(5R)-5-hydroxytriptolide (LLDT-8), a novel immunosuppressant in clinical trials, exhibits potent antitumor activity via transcription inhibition".CANCER LETTERS 324.1(2012):75-82.