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

• Published in: Molecular cancer Vol. 9; no. 1; p. 276
• Main Authors: Yu, Danny C W, Waby, Jennifer S, Chirakkal, Haridasan, Staton, Carolyn A, Corfe, Bernard M
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 15-10-2010; BioMed Central; BMC
• Subjects: Angiogenesis; Apoptosis; Butyrates - pharmacology; Caco-2 Cells; Cancer therapies; Cell cycle; Cell receptors; Colleges & universities; Colon; Colon cancer; Colonic Neoplasms - genetics; Colonic Neoplasms - metabolism; Colonic Neoplasms - prevention & control; Colorectal cancer; Drug therapy; Electrophoretic Mobility Shift Assay; Enzyme-Linked Immunosorbent Assay; Experiments; Gene Expression Regulation - drug effects; HCT116 Cells; Health aspects; Histone Deacetylase Inhibitors - pharmacology; HT29 Cells; Humans; Immunoblotting; Ligands; Neuropilin-1 - genetics; Neuropilin-1 - metabolism; Physiological aspects; Proteins; Reverse Transcriptase Polymerase Chain Reaction; RNA, Small Interfering - genetics; RNA, Small Interfering - physiology; Sp1 Transcription Factor - genetics; Sp1 Transcription Factor - metabolism; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - genetics; Vascular Endothelial Growth Factor A - metabolism; United Kingdom
• ISSN: 1476-4598; 1476-4598
• DOI: 10.1186/1476-4598-9-276

Neuropilin 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.
Here 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.
The downregulation of the key apoptotic and angiogenesis regulator NRP-1 by butyrate suggests a novel contributory mechanism to the chemopreventive effect of dietary fibre.