Hirsutenone inhibits phorbol ester-induced upregulation of COX-2 and MMP-9 in cultured human mammary epithelial cells: NF-kappa B as a potential molecular target
- Authors
- Kim, JH; Lee, KW; Lee, MW; Lee, HJ; Kim, SH; Surh, YJ
- Issue Date
- 23-Jan-2006
- Publisher
- ELSEVIER SCIENCE BV
- Keywords
- hirsutenone; cyclooxygenase-2; matrix metalloprotemase-9; human breast epithelial cells; nuclear factor kappa B; invasion; migration
- Citation
- FEBS LETTERS, v.580, no.2, pp 385 - 392
- Pages
- 8
- Journal Title
- FEBS LETTERS
- Volume
- 580
- Number
- 2
- Start Page
- 385
- End Page
- 392
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/24428
- DOI
- 10.1016/j.febslet.2005.12.051
- ISSN
- 0014-5793
1873-3468
- Abstract
- Inappropriate upregulation of cyclooxygenase-2 (COX-2) and matrix metalloproteinases (MMPs) has been implicated in the pathogenesis of various types of cancer. In the present study, we investigated the effects of hirsutenone, a diarylheptanoid isolated from the medicinal plant Alnus hirsuta var. sibirica, on the expression of COX-2 and MMP-9 induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) in MCF10A human breast epithelial cells. Treatment of MCF10A cells with TPA led to the upregulation of COX-2 and MMP-9. Hirsutenone at 12 mu M inhibited the TPA-induced COX-2 expression at both the transcriptional and posttranscriptional levels. Hirsutenone also suppressed the synthesis of prostaglandin E-2, one of the major products of COX-2, and its catalytic activity. The upregulation of MMP-9 by TPA was also significantly reduced by hirsutenone. Likewise, hirsutenone attenuated the invasiveness and motility of MCF10A cells stimulated with TPA. Hirsutenone blocked the TPA-induced DNA binding of nuclear factor kappa B (NF-kappa B) and translocation of p65, the functionally active NF-kappa B subunit, to the nucleus. The luciferase reporter gene assay revealed that hirsutenone abrogated the transcriptional activity of NF-kappa B. Treatment of MCF10A cells with N-alpha-TOSYI-L-phenylaianine chloromethyl ketone, a specific inhibitor of NF-kappa B, reduced the TPA-induced expression of COX-2 and MMP-9. In summary, hirsutenone inhibits the TPA-induced upregulation of COX-2 and MMP-9 in human breast epithelial cells, possibly by targeting NF-kappa B, which may contribute to its chemopreventive effects. (c) 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
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