Babykutty, SubojPriya, P. S.Nandini, R. J.Kumar, M. A. SureshNair, Mangalam S.Srinivas, PriyaGopala, Srinivas2012-12-042012-12-042012MOLECULAR CARCINOGENESIS. 51; 6; 475-490http://dx.doi.org/10.1002/mc.20812https://dspace.sctimst.ac.in/handle/123456789/795Nimbolide, 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.Oncology