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Inappropriateupregulationofcyclooxygenase-2(COX-2)andmatrixmetalloproteinases(MMPs)ha... 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 MCF 10A human breast epithelial cells. Treatment of MCF 10A 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 MCF 10A 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 MCF 10A 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. 展开
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mumuaxx
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治疗不当的COX-2 cyclooxygenase-2()和基质金属蛋白酶(MMPs)已经被牵涉在发病的各种类型的癌症。在目前的研究中,我们考察了影响diarylheptanoid hirsutenone隔绝,药用植物Alnus hirsuta var. sibirica COX-2的表现上,诱导肿瘤和MMP-9 12-O-tetradecanoylphorbol-13-acetate(TPA)子10A MCF人类乳腺上皮细胞。治疗MCF 10A细胞治疗导致的30 COX-2和MMP-9。在十二亩米Hirsutenone抑制TPA-induced COX-2表现在转录和逆境的水平。合成Hirsutenone抑制了前列腺素E-2之一,主要产品的COX-2,其催化活性。通过对MMP-9治疗的发病率也显著降低30 hirsutenone。同样,削弱侵入性及运动的hirsutenone MCF细胞的刺激和30 10A)。Hirsutenone TPA-induced DNA结合阻碍了核转录因子卡巴(B)和易位NF-kappa p65、功能活跃的单位,B NF-kappa细胞核。这个luciferase基因分析法显示的转录活性hirsutenone废除NF-kappa B细胞治疗MCF N-alpha-TOSYI-L-phenylaianine chloromethyl 10A酮、一个特定的乙酰胆碱酯酶抑制剂,B,降低了TPA-induced NF-kappa COX-2表达和MMP-9。综上所述,hirsutenone TPA-induced COX-2治疗抑制了对人类和MMP -9乳腺上皮细胞,可能是针对NF-kappa B,这也有助于其chemopreventive效果。2005年的联合会(c)的欧洲生物技术协会。出版社发表。版权所有。
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