Butyrate suppresses expression of neuropilin I in colorectal cell lines through inhibition of Sp1 transactivation

Molecular Cancer

Research

Bernard M Corfe¹  Danny CW Yu¹  Carolyn A Staton¹  Haridasan Chirakkal¹  Jennifer S Waby² 

[1] Department of Oncology, School of Medicine and Biomedical Sciences, University of Sheffield, Royal Hallamshire Hospital, S10 2JF, Sheffield, UK;Department of Oncology, School of Medicine and Biomedical Sciences, University of Sheffield, Royal Hallamshire Hospital, S10 2JF, Sheffield, UK;Department of Biological Sciences, The University of Hull, HU6 7RX, UK;

关键词: Vascular Endothelial Growth Factor;    Butyrate;    HCT116 Cell;    Colon Cancer Cell Line;    Sodium Butyrate;   

DOI  :  10.1186/1476-4598-9-276

 received in 2009-12-21, accepted in 2010-10-15,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundNeuropilin is a transmembrane receptor for vascular endothelial growth factor (VEGF) and is expressed in normal endothelial cells and upregulated in cancer cells. Neuropilin-1 (NRP-1) has been shown to promote tumour cell migration and survival in colon cancer in response to VEGF binding. The expression profiles of neuropilins, associated co-receptors and known ligands have been mapped in three colorectal cell lines: Caco-2, HCT116 & HT29. We have previously shown that butyrate, a naturally occurring histone deacetylase inhibitor (HDACi) produced by fermentation of fibre in the colon, causes apoptosis of colon cancer cell lines.ResultsHere we demonstrate that butyrate down-regulates NRP-1 and VEGF at the mRNA and protein level in colorectal cancer cell lines. NRP-1 is a known transcriptional target of Sp1, whose activity is regulated by acetylation. NRP-1 down-regulation by butyrate was associated with decreased binding affinity of Sp1 for canonical Sp-binding sites in the NRP-1 promoter. siRNA-mediated knock-down of Sp1 implied that Sp1 may have strong DNA binding activity but weak transactivation potential.ConclusionThe downregulation of the key apoptotic and angiogenesis regulator NRP-1 by butyrate suggests a novel contributory mechanism to the chemopreventive effect of dietary fibre.

【 授权许可】

Unknown   
© Yu et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.