Calagualine inhibits nuclear transcription factors-κB activated by various inflammatory and tumor promoting agents
- 作者：Manna ; Sunil K. ; Bueso-Ramos ; Carlos ; Alvarado ; Francisco ; Aggarwal ; Bharat B.
- 关键词：Nuclear transcription factor-κ ; B ; Calagualine ; Tumor necrosis factor ; Tumor promoters ; Inflammation ; LPS ; TNF ; tumor necrosis factor ; NF-κ ; B ; nuclear transcription factor-κ ; B ; AP-1 ; activator protein-1 ; Iκ ; B ; inhibitory subunit of NF-κ
- 刊名：Cancer Letters
- 出版年：2003
- 期刊代码：44_03043835
- 类别：med
- 出版时间：February 20, 2003
- 卷：190
- 期：2
- 页码：171-182
- 文件大小：402 K
摘要
Calagualine derived from the fern of the genus Polypodium, commonly called calaguala, has had clinically documented medicinal uses in South America and Spain and been shown to block tumor metastasis, proliferation, and inflammation, all known to require the activation of nuclear transcription factor-κB (NF-κB). Therefore, we investigated the effect of calagualine on NF-κB activation induced by various inflammatory and tumor promoting agents. Calagualine blocked tumor necrosis factor (TNF)-induced activation of NF-κB through inhibition of phosphorylation and degradation of IκBα, an inhibitor of NF-κB. The effects of calagualine were not cell type-specific, as it blocked TNF-induced NF-κB activation in a variety of cells. NF-κB-dependent reporter gene transcription activated by TNF was also suppressed by calagualine. The TNF-induced NF-κB activation cascade involving TNFR1-TNF receptor-associated death domain-TNF receptor-associated factor 2 (TRAF2)-NF-κB-inducing kinase (NIK)-IκBα kinase was interrupted at the TRAF2 and NIK sites by calagualine, which would account for its suppression of NF-κB reporter gene expression. Calagualine blocked NF-κB activation induced by phorbol ester and lipopolysaccharide. Overall our results indicate that calagualine inhibits activation of NF-κB and this may provide a molecular basis for calagualine's ability to suppress inflammation and tumorigenesis.