alexa 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-κB in colon cancer cells.


Journal of Addiction Research & Therapy

Author(s): Babykutty S, S PP, J NR, Kumar MA, Nair MS,

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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-κB, which is an important transcription factor for controlling MMP-2/9 and VEGF gene expression. Copyright © 2011 Wiley Periodicals, Inc. This article was published in Mol Carcinog and referenced in Journal of Addiction Research & Therapy

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