Anti-inflammatory Effect of Pitavastatin on NF-.KAPPA.B Activated by TNF-.ALPHA. in Hepatocellular Carcinoma Cells
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- Wang Juyong
- Department of Clinical Laboratory Medicine, Faculty of Medicine, Toyama University
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- Tokoro Takashi
- Department of Clinical Laboratory Medicine, Faculty of Medicine, Toyama University
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- Higa Susumu
- Department of Clinical Laboratory Medicine, Faculty of Medicine, Toyama University
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- Kitajima Isao
- Department of Clinical Laboratory Medicine, Faculty of Medicine, Toyama University
Bibliographic Information
- Other Title
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- Anti-inflammatory Effect of Pitavastatin on NF-kB Activated by TNF-α in Hepatocellular Carcinoma Cells
- Anti inflammatory Effect of Pitavastatin on NF kB Activated by TNF アルファ in Hepatocellular Carcinoma Cells
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Abstract
As nuclear factor-kappa B (NF-κB) is essential for promoting inflammation-associated cancer, it is a potential target for cancer prevention in chronic inflammatory diseases. Here we examined the anti-inflammatory effect of pitavastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, on NF-κB activated by TNF-α in hepatocellular carcinoma (HCC) cells. Western blot revealed that the treatment of Huh 7 cells with pitavastatin at 0.1 μM inhibited the nuclear expression of NF-κB p65 induced by TNF-α. Furthermore, electrophoretic mobility shift assay showed that after the cells were incubated with pitavastatin alone or with pitavastatin and TNF-α for 24 h, pitavastatin significantly decreased the DNA binding activity of NF-κB induced by TNF-α. Subsequently, luciferase assay revealed that pitavastatin suppressed the transcriptional activity of the NF-κB promoter, which was clearly related to the HMG-CoA reductase activity because the addition of mevalonic acid (MEV) elevated the TNF-α activity. Moreover, the Rho kinase inhibitor Y27632 had no major effect on the NF-κB inhibitory activity of pitavastatin. The inhibitory effect of pitavastatin is possibly independent of the Rho kinase pathway in inflammation-associated HCC cells is. Finally, the addition of TNF-α significantly increased IL-6 protein production, which was suppressed by the addition of pitavastatin. These results suggest that pitavastatin at a low dose (0.1 μM) inhibits NF-κB activation and decreases IL-6 production induced by TNF-α, and is therefore expected to be a new strategy for treating HCC.
Journal
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- Biological and Pharmaceutical Bulletin
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Biological and Pharmaceutical Bulletin 29 (4), 634-639, 2006
The Pharmaceutical Society of Japan
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Keywords
Details 詳細情報について
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- CRID
- 1390282679604624768
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- NII Article ID
- 110005602161
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- NII Book ID
- AA10885497
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- ISSN
- 13475215
- 09186158
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- NDL BIB ID
- 7861425
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- Text Lang
- en
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- Data Source
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- JaLC
- NDL
- Crossref
- CiNii Articles
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- Abstract License Flag
- Disallowed