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|Title:||Nimbolide retards tumor cell migration, invasion, and angiogenesis by downregulating MMP-2/9 expression via inhibiting ERK1/2 and reducing DNA-binding activity of NF-kappa B in colon cancer cells|
Priya, P. S.
Nandini, R. J.
Kumar, M. A. Suresh
Nair, Mangalam S.
|Citation:||MOLECULAR CARCINOGENESIS. 51; 6; 475-490|
|Abstract:||Nimbolide, a plant-derived limonoid has been shown to exert its antiproliferative effects in various cell lines. We demonstrate that nimbolide effectively inhibited proliferation of WiDr colon cancer cells through inhibition of cyclin A leading to S phase arrest. It also caused activation of caspase-mediated apoptosis through the inhibition of ERK1/2 and activation of p38 and JNK1/2. Further nimbolide effectively retarded tumor cell migration and invasion through inhibition of metalloproteinase-2/9 (MMP-2/9) expression, both at the mRNA and protein level. It was also a strong inhibitor of VEGF expression, promoter activity, and in vitro angiogenesis. Finally, nimbolide suppressed the nuclear translocation of p65/p50 and DNA binding of NF-?B, which is an important transcription factor for controlling MMP-2/9 and VEGF gene expression. (C) 2011 Wiley Periodicals, Inc.|
|Appears in Collections:||Journal Articles|
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