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Prevention Research 6: Molecular Markers in Prevention Research
Abstract #3162
Functional food ingredients against colorectal cancer.
Marjan J. Van Erk, Cyrille Krul, Eric Caldenhoven, Rob H. Stierum, Ruud A. Woutersen and Ben Van Ommen
Wageningen University, Wageningen, Netherlands, TNO Nutrition and Food Research, Zeist, Netherlands, Numico Research, Wageningen, Netherlands
The scientific consensus is that most cancers are largely preventable, and one of the most effective means of reducing risk or prevention is consumption of appropriate diets. It has been estimated that 66-75% of the worldwide occurring gastrointestinal tract cancers are preventable by the diet, globally.
For example, high consumption of fruits and vegetables has been associated with reduced risk of colorectal cancer.
Great efforts have been made to identify cancer-preventive components both in our diet in general and in fruits and vegetables in particular, and to identify mechanisms of prevention of these components. We developed in vitro bioassays to evaluate the possible efficacy of functional food ingredients in prevention or inhibition of the development of colon cancer.
Cell line experiments were combined with cDNA microarrays to study the effects of food compounds on expression of thousands of genes and to search for differentially expressed genes which could serve as molecular markers possibly involved in cancer formation and prevention.
Extended bioinformatics was applied to search for potential biochemical and cellular pathway-supported markers of anti-carcinogenesis. First we compared gene expression profiles of 14 different human colon cancer cell lines. These expression profiles were compared with expression profiles of colon biopsies from normal and tumor tissue of the same individual by use of principal component analysis.
Secondly, based on the microarray results and on literature information on the cell lines, four cell lines were selected for further investigations. These four cell lines (NCM460, HT29, Caco-2 and T84) were used to study multiple gene expression patterns induced by various food components. From these fingerprint profiles both compound specific and more general mechanisms involved in prevention against onset and development of colon cancer could be elucidated.
Plant components that were studied included quercetin, curcumin and resveratrol. These compounds were found to protect against development of colon cancer in both in vitro and in vivo studies. Effects of these compounds on expression profiles of colon cancer cells lines will be demonstrated and related to physiological data, such as cell cycle and apoptosis.
For example, cell cycle arrest in HT29 cells in response to curcumin is related to changes in expression of cell cycle genes.
Despite the limitations of in vitro models, the results obtained demonstrate that the use of transcriptomics and other ‘omics’ technologies in in vitro research can yield very useful information on nutrient-gene interaction.
Proc Amer Assoc Cancer Res, Volume 45, 2004
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