In:
Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 13, No. 7 ( 2007-04-01), p. 2290-2297
Abstract:
Purpose: Morin is a flavone that exhibits antiproliferative, antitumor, and anti-inflammatory effects through a mechanism that is not well understood. Because of the role of transcription factor nuclear factor-κB (NF-κB) in the control of cell survival, proliferation, tumorigenesis, and inflammation, we postulated that morin mediates its effects by modulating NF-κB activation. Experimental Design: We investigated the effect of morin on NF-κB pathway activated by inflammatory agents, carcinogens, and tumor promoters. The effect of this flavone on expression of NF-κB–regulated gene products involved in cell survival, proliferation, and invasion was also examined. Results: We showed by DNA-binding assay that NF-κB activation induced by tumor necrosis factor (TNF), phorbol 12-myristate 13-acetate, lipopolysaccharide, ceramide, interleukin-1, and H2O2 was suppressed by morin; the suppression was not cell type specific. The suppression of NF-κB by morin was mediated through inhibition of IκBα (inhibitory subunit of NF-κB) kinase, leading to suppression of phosphorylation and degradation of IκBα and consequent p65 nuclear translocation. Morin also inhibited the NF-κB–dependent reporter gene expression activated by TNF, TNF receptor (TNFR) 1, TNFR1-associated death domain, TNFR-associated factor 2, NF-κB–inducing kinase, IκB kinase, and the p65 subunit of NF-κB. NF-κB–regulated gene products involved in cell survival [inhibitor of apoptosis (IAP) 1, IAP2, X chromosome-linked IAP, Bcl-xL, and survivin], proliferation (cyclin D1 and cyclooxygenase-2), and invasion (matrix metalloproteinase-9) were down-regulated by morin. These effects correlated with enhancement of apoptosis induced by TNF and chemotherapeutic agents. Conclusion: Overall, our results indicate that morin suppresses the activation of NF-κB and NF-κB–regulated gene expression, leading to enhancement of apoptosis. This may provide the molecular basis for the ability of morin to act as an anticancer and anti-inflammatory agent.
Type of Medium:
Online Resource
ISSN:
1078-0432
,
1557-3265
DOI:
10.1158/1078-0432.CCR-06-2394
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2007
detail.hit.zdb_id:
1225457-5
detail.hit.zdb_id:
2036787-9
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