Comprehensive evaluation of a novel nuclear factor-κB inhibitor, quinoclamine, by transcriptomic analysis

中國醫藥大學機構典藏 China Medical University Repository, Taiwan > 中醫學院 > 中國醫學研究所 > 期刊論文 > Item 310903500/5470

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题名:	Comprehensive evaluation of a novel nuclear factor-κB inhibitor, quinoclamine, by transcriptomic analysis
作者:	鄭文裕(Cheng, W.Y.);連金城(Lien Jin Cherng);項千芸(Chien-Yun Hsiang);吳世祿(Shih-Lu Wu);李佳橙(Chia-Cheng Li);羅欣宜(Hsin-Yi Lo);陳兆群(Jaw-Chyun Chen);江素瑛(Su-yin Chiang);梁基安(Ji-An Liang);侯庭鏞(Tin-Yun Ho)*
贡献者:	中醫學院中國醫學研究所
关键词:	quinoclamine;nuclear factor-κB;microarray;cell cycle;UDP glucuronosyltransferases
日期:	2009-07
上传时间:	2009-08-24 14:47:07 (UTC+8)
摘要:	Background and purpose: The transcription factor nuclear factor-κB (NF-κB) has been linked to the cell growth, apoptosis and cell cycle progression. NF-κB blockade induces apoptosis of cancer cells. Therefore, NF-κB is suggested as a potential therapeutic target for cancer. Here, we have evaluated the anti-cancer potential of a novel NF-κB inhibitor, quinoclamine (2-amino-3-chloro-1,4-naphthoquinone). Experimental approach: In a large-scale screening test, we found that quinoclamine was a novel NF-κB inhibitor. The global transcriptional profiling of quinoclamine in HepG2 cells was therefore analysed by transcriptomic tools in this study. Key results: Quinoclamine suppressed endogenous NF-κB activity in HepG2 cells through the inhibition of IκB-α phosphorylation and p65 translocation. Quinoclamine also inhibited induced NF-κB activities in lung and breast cancer cell lines. Quinoclamine-regulated genes interacted with NF-κB or its downstream genes by network analysis. Quinoclamine affected the expression levels of genes involved in cell cycle or apoptosis, suggesting that quinoclamine exhibited anti-cancer potential. Furthermore, quinoclamine down-regulated the expressions of UDP glucuronosyltransferase genes involved in phase II drug metabolism, suggesting that quinoclamine might interfere with drug metabolism by slowing down the excretion of drugs. Conclusion and implications: This study provides a comprehensive evaluation of quinoclamine by transcriptomic analysis. Our findings suggest that quinoclamine is a novel NF-κB inhibitor with anti-cancer potential.
關聯:	BRITISH JOURNAL OF PHARMACOLOGY 157(5)746 ~756
显示于类别:	[中國醫學研究所] 期刊論文

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