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

W. Y. Cheng, J. C. Lien, C. Y. Hsiang, S. L. Wu, C. C. Li, H. Y. Lo, J. C. Chen, S. Y. Chiang, J. A. Liang, T. Y. Ho

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Background and purpose: The transcription factor nuclear factor-KB (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 Il 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 suqqest that quinoclamine is a novel NF-κB inhibitor with anti-cancer potential.

Original languageEnglish
Pages (from-to)746-756
Number of pages11
JournalBritish Journal of Pharmacology
Volume157
Issue number5
DOIs
Publication statusPublished - Jul 2009
Externally publishedYes

Fingerprint

Hep G2 Cells
Neoplasms
Apoptosis
2-amino-3-chloro-1,4-naphthoquinone
Cell Cycle
Pharmaceutical Preparations
Glucuronosyltransferase
Gene Regulatory Networks
Genes
Lung Neoplasms
Transcription Factors
Phosphorylation
Breast Neoplasms
Gene Expression
Cell Line
Growth
Therapeutics

Keywords

  • Cell cycle
  • Microarray
  • Nuclear factor-κB
  • Quinoclamine
  • UDP glucuronosyltransferases

ASJC Scopus subject areas

  • Pharmacology

Cite this

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

In: British Journal of Pharmacology, Vol. 157, No. 5, 07.2009, p. 746-756.

Research output: Contribution to journalArticle

Cheng, WY, Lien, JC, Hsiang, CY, Wu, SL, Li, CC, Lo, HY, Chen, JC, Chiang, SY, Liang, JA & Ho, TY 2009, 'Comprehensive evaluation of a novel nuclear factor-κB inhibitor, quinoclamine, by transcriptomic analysis', British Journal of Pharmacology, vol. 157, no. 5, pp. 746-756. https://doi.org/10.1111/j.1476-5381.2009.00223.x
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. / Comprehensive evaluation of a novel nuclear factor-κB inhibitor, quinoclamine, by transcriptomic analysis. In: British Journal of Pharmacology. 2009 ; Vol. 157, No. 5. pp. 746-756.
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AU - Wu, S. L.

AU - Li, C. C.

AU - Lo, H. Y.

AU - Chen, J. C.

AU - Chiang, S. Y.

AU - Liang, J. A.

AU - Ho, T. Y.

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N2 - Background and purpose: The transcription factor nuclear factor-KB (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 Il 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 suqqest that quinoclamine is a novel NF-κB inhibitor with anti-cancer potential.

AB - Background and purpose: The transcription factor nuclear factor-KB (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 Il 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 suqqest that quinoclamine is a novel NF-κB inhibitor with anti-cancer potential.

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