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- Title
Comprehensive evaluation of a novel nuclear factor-kappaB inhibitor, quinoclamine, by transcriptomic analysis.
- Authors
Cheng, W.-Y.; Lien, J.-C.; Hsiang, C.-Y.; Wu, S.-L.; Li, C.-C.; Lo, H.-Y.; Chen, J.-C.; Chiang, S.-Y.; Liang, J.-A.; Ho, T.-Y.
- Abstract
<bold>Background and Purpose: </bold>The transcription factor nuclear factor-kappaB (NF-kappaB) has been linked to the cell growth, apoptosis and cell cycle progression. NF-kappaB blockade induces apoptosis of cancer cells. Therefore, NF-kappaB is suggested as a potential therapeutic target for cancer. Here, we have evaluated the anti-cancer potential of a novel NF-kappaB inhibitor, quinoclamine (2-amino-3-chloro-1,4-naphthoquinone).<bold>Experimental Approach: </bold>In a large-scale screening test, we found that quinoclamine was a novel NF-kappaB inhibitor. The global transcriptional profiling of quinoclamine in HepG2 cells was therefore analysed by transcriptomic tools in this study.<bold>Key Results: </bold>Quinoclamine suppressed endogenous NF-kappaB activity in HepG2 cells through the inhibition of IkappaB-alpha phosphorylation and p65 translocation. Quinoclamine also inhibited induced NF-kappaB activities in lung and breast cancer cell lines. Quinoclamine-regulated genes interacted with NF-kappaB 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.<bold>Conclusion and Implications: </bold>This study provides a comprehensive evaluation of quinoclamine by transcriptomic analysis. Our findings suggest that quinoclamine is a novel NF-kappaB inhibitor with anti-cancer potential.
- Subjects
TRANSCRIPTION factors; DRUG metabolism -- Evaluation; CANCER cells; BIOCHEMISTRY; CELL culture; GLYCOSYLTRANSFERASES; PROTEIN metabolism; ANTINEOPLASTIC agents; APOPTOSIS; BIOLOGICAL transport; CELL cycle; CELL lines; CELL physiology; COMPARATIVE studies; DOSE-effect relationship in pharmacology; GENES; GENETIC techniques; RESEARCH methodology; MEDICAL cooperation; MOLECULAR structure; PHOSPHORYLATION; QUINONE; RESEARCH; TRANSFERASES; DNA-binding proteins; EVALUATION research; OLIGONUCLEOTIDE arrays; GENE expression profiling; CHEMICAL inhibitors; PHARMACODYNAMICS
- Publication
British Journal of Pharmacology, 2009, Vol 157, Issue 5, p746
- ISSN
0007-1188
- Publication type
journal article
- DOI
10.1111/j.1476-5381.2009.00223.x