کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10767174 | 1050698 | 2008 | 6 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
A citrus polymethoxyflavonoid, nobiletin, is a novel MEK inhibitor that exhibits antitumor metastasis in human fibrosarcoma HT-1080 cells
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کلمات کلیدی
MMP12-O-tetradecanoyl phorbol 13-acetatemitogen-activated protein/extracellular signal-regulated kinaseHEPTPBS(−)PKCECLpKaERKtPAenhanced chemiluminescence - بهبود شیمیایی لومنEagle’s Minimum Essential Medium - حداقل ضروری متوسط عقابFlavonoid - فلاونوئیدmatrix metalloproteinase - ماتریکس متالوپروتئینازMEM - مامانMEK - مجاهدین خلقNobiletin - نوبیلتینProtein kinase C - پروتئین کیناز سیExtracellular regulated kinases - کیناز تنظیم شده خارج سلولیp21-activated kinase - کیناز فعال p21
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: A citrus polymethoxyflavonoid, nobiletin, is a novel MEK inhibitor that exhibits antitumor metastasis in human fibrosarcoma HT-1080 cells A citrus polymethoxyflavonoid, nobiletin, is a novel MEK inhibitor that exhibits antitumor metastasis in human fibrosarcoma HT-1080 cells](/preview/png/10767174.png)
چکیده انگلیسی
The activation of mitogen-activated protein/extracellular signal-regulated kinase (MEK) is well known to be associated with tumor invasion and metastasis. We previously reported that a polymethoxyflavonoid, nobiletin (5,6,7,8,3â²,4â²-hexamethoxyflavone), derived from Citrus depressa (Hayata), inhibits the phosphorylation of MEK and thereby suppresses matrix metalloproteinase (MMP) expression in a tumor-metastasis stimulator, 12-O-tetradecanoyl phorbol 13-acetate (TPA)-stimulated human fibrosarcoma HT-1080 cells [Mol. Cancer Ther. 3 (2004) 839-847]. In the present study, we investigated whether or not nobiletin might directly influence MEK activity to exhibit the antitumor metastatic activity in vitro. MEK kinase assay using myelin basic protein (MBP) revealed that TPA-augmented MEK activity in HT-1080 cells and that the augmented MEK activity was diminished by nobiletin treatment. In addition, the decrease in MEK activity caused by nobiletin was found to inhibit the phosphorylation of extracellular regulated kinases (ERK), a downstream signaling factor for MEK. Furthermore, when an immunoprecipitated active MEK was incubated with nobiletin under cell-free conditions, nobiletin was found to inhibit the MEK-mediated MBP phosphorylation. In contrast, other citrus polymethoxyflavonoids such as 3-hydroxy-5,6,7,8,3â²,4â²-hexamethoxyflavone (natsudaidain) and 3,5,6,7,8,3â²,4â²-heptamethoxyflavone, did not directly inhibit MEK activity. Moreover, natsudaidain and 3,5,6,7,8,3â²,4â²-heptamethoxyflavone exhibited no or less inhibitory effect than nobiletin on the proMMP-9/progelatinase B production in HT-1080 cells. Therefore, these results provide novel evidence that nobiletin directly inhibits MEK activity and decreases the sequential phosphorylation of ERK, exhibiting the antitumor metastatic activity by suppressing MMP expression in HT-1080 cells.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 366, Issue 1, 1 February 2008, Pages 168-173
Journal: Biochemical and Biophysical Research Communications - Volume 366, Issue 1, 1 February 2008, Pages 168-173
نویسندگان
Yoshiki Miyata, Takashi Sato, Keisuke Imada, Akira Dobashi, Masamichi Yano, Akira Ito,