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-kB in colon cancer cells

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


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.

Similar Articles

Nitric oxide represses inhibitory kappaB kinase through S-nitrosylation

Author(s): Reynaert NL, Ckless K, Korn SH, Vos N, Guala AS, et al.

Signaling by distinct classes of phosphoinositide 3-kinases

Author(s): Vanhaesebroeck B, Waterfield MD

Activation of Akt/protein kinase B overcomes a G(2)/m cell cycle checkpoint induced by DNA damage

Author(s): Kandel ES, Skeen J, Majewski N, Di Cristofano A, Pandolfi PP, et al.

Induction of cell cycle arrest and apoptosis in human breast cancer cells by quercetin

Author(s): Choi JA, Kim JY, Lee JY, Kang CM, Kwon HJ, et al.

Protein measurement with the Folin phenol reagent

Author(s): Lowry OH, Rosebrough NJ, Farr AL, Randall RJ

Garlic compound, diallyl disulfide induces cell cycle arrest in prostate cancer cell line PC-3

Author(s): Arunkumar A, Vijayababu MR, Srinivasan N, Aruldhas MM, Arunakaran J