Carcinogenesis Advance Access published online on September 9, 2004
Carcinogenesis, doi:10.1093/carcin/bgh265
© 2004 by Oxford University Press
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Institute of General Pathology, Catholic University - L.go F. Vito, 1 - 00168 Rome, Italy
* To whom correspondence should be addressed. E-mail: g.calviello{at}rm.unicatt.it.
n-3 Polyunsaturated fatty acids (PUFAs) inhibit the development of microvessels in mammary tumors growing in mice. Human colorectal tumors produce vascular endothelial growth factor (VEGF) whose expression is up-regulated in tumor cells by both cyclooxygenase-2 (COX-2) and PGE2 and directly correlated to neoangiogenesis and clinical outcome. The goal of this study was to examine the capability of n-3 PUFAs to regulate Vascular Endothelial Growth Factor (VEGF) expression in HT-29 human colorectal cells in vitro and in vivo. Constitutive VEGF expression was augmented in cultured HT-29 cells by serum starvation and the effects of eicosapentaenoic (EPA) or docosahexaenoic acid (DHA) on VEGF, COX-2, phosphorylated extracellular signal- regulated kinase (ERK)-1 and -2 and (hypoxia-inducible-factor1-
Revised July 15, 2004
Accepted August 10, 2004
CANCER BIOLOGY
n-3 PUFAs reduce VEGF expression in human colon cancer cells modulating the COX-2/ PGE2 induced ERK-1 and -2 and HIF-1
induction pathway
2 Institute of Pathology, Catholic University - L.go F. Vito, 1 - 00168 Rome, Italy
3 Institute of Pharmacology, Catholic University - L.go F. Vito, 1 - 00168 Rome, Italy
4 Institute of Histology, Catholic University - L.go F. Vito, 1 - 00168 Rome, Italy
Abstract 
) HIF-1 expression and PGE2 levels were assessed. Tumor growth, VEGF, COX and PGE2 analysis were carried out in tumors derived from HT-29 cells transplanted in nude mice fed with either EPA or DHA. Both EPA and DHA reduced VEGF and COX-2 expression and PGE2 levels in HT-29 cells cultured in vitro. Moreover, they inhibited ERK-1 and -2 phosphorylation and HIF-1 protein overexpression, critical steps in the PGE2-induced signalling pathway leading to the augmented expression of VEGF in colon cancer cells. EPA showed always higher efficacy than DHA in vitro. Both fatty acids decreased the growth of the tumors obtained by inoculating HT-29 cells in nude mice, microvessel formation and the levels of VEGF, COX-2 and PGE2 in tumors. These data provide evidence that these n-3 PUFAs are able to inhibit VEGF expression in colon cancer cells and suggest that one possible mechanism involved may be the negative regulation of the COX-2/PGE2 pathway. Their potential clinical application as anti-angiogenic compounds in colon cancer therapy is proposed.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  E. R. Tuller, C. T. Beavers, J. R. Lou, M. A. Ihnat, D. M. Benbrook, and W.-Q. Ding Docosahexaenoic Acid Inhibits Superoxide Dismutase 1 Gene Transcription in Human Cancer Cells: The Involvement of Peroxisome Proliferator-Activated Receptor {alpha} and Hypoxia-Inducible Factor-2{alpha} Signaling Mol. Pharmacol., September 1, 2009; 76(3): 588 - 595. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Calviello, F. Resci, S. Serini, E. Piccioni, A. Toesca, A. Boninsegna, G. Monego, F. O. Ranelletti, and P. Palozza Docosahexaenoic acid induces proteasome-dependent degradation of {beta}-catenin, down-regulation of survivin and apoptosis in human colorectal cancer cells not expressing COX-2 Carcinogenesis, June 1, 2007; 28(6): 1202 - 1209. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Colas, K. Maheo, F. Denis, C. Goupille, C. Hoinard, P. Champeroux, F. Tranquart, and P. Bougnoux Sensitization by dietary docosahexaenoic Acid of rat mammary carcinoma to anthracycline: a role for tumor vascularization. Clin. Cancer Res., October 1, 2006; 12(19): 5879 - 5886. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Friesen and S. M. Innis Maternal dietary fat alters amniotic fluid and fetal intestinal membrane essential n-6 and n-3 fatty acids in the rat Am J Physiol Gastrointest Liver Physiol, March 1, 2006; 290(3): G505 - G510. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Matsuyama, H. Mitsuyama, M. Watanabe, K.-i. Oonakahara, I. Higashimoto, M. Osame, and K. Arimura Effects of Omega-3 Polyunsaturated Fatty Acids on Inflammatory Markers in COPD Chest, December 1, 2005; 128(6): 3817 - 3827. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. C. Karlsson, U. Huss, A. Jenner, B. Halliwell, L. Bohlin, and J. J. Rafter Human Fecal Water Inhibits COX-2 in Colonic HT-29 Cells: Role of Phenolic Compounds J. Nutr., October 1, 2005; 135(10): 2343 - 2349. [Abstract] [Full Text] [PDF]
|
|