Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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Record number 370512
Title Pathway and single gene analyses of inhibited Caco-2 differentiation by ascorbate-stabilized quercetin suggest enhancement of cellular processes associated with development of colon cancer
Author(s) Dihal, A.A.; Tilburgs, C.; Erk, M.J. van; Rietjens, I.M.C.M.; Woutersen, R.A.; Stierum, R.H.
Source Molecular Nutrition & Food Research 51 (2007)8. - ISSN 1613-4125 - p. 1031 - 1045.
Department(s) Sub-department of Toxicology
Chair Nutrition Metabolism and Genomics
Publication type Refereed Article in a scientific journal
Publication year 2007
Keyword(s) metabolizing enzyme expression - surfactant-like particles - human colorectal-cancer - line caco-2 - in-vitro - cells - flavonoids - proliferation - progression - profiles
Abstract The aim was to investigate mechanisms contributing to quercetin's previously described effects on cell-proliferation and -differentiation, which contradicted its proposed anticarcinogenic potency. in a 10-day experiment, 40 mu M quercetin stabilized by I mM ascorbate reduced Caco-2 differentiation up to 50% (p <0.001). Caco-2 RNA from days 5 and 10, hybridized on HG-U133A2.0Affymetrix Gene Chips(circle dot), showed 1743 affected genes on both days (p <0.01). All 14 Caco-2 differentiation-associated genes showed decreased expression (p <0.01), including intestinal alkaline phosphatase, that was confirmed technically (qRT-PCR) and functionally (enzyme-activity). The 1743 genes contributed to 27 pathways (p <0.05) categorized under six gene ontology (GO) processes, including apoptosis and cell-cycle. Genes within these GO-processes showed fold changes that suggest increased cell-survival and -proliferation. Furthermore, quercetin down-regulated expression of genes involved in tumor-suppression and phase 11 metabolism, and up-regulated oncogenes. Gene expression changes mediated by ascorbate-stabilized quercetin were concordant with those occurring in human colorectal carcinogenesis (approximate to 80-90%), but were opposite to those previously described for Caco-2 cells exposed to quercetin without ascorbate (approximate to 75-90%). In conclusion, gene expression among Caco-2 cells exposed to ascorbate-stabilized quercetin showed mechanisms contrary to what is expected for a cancer-preventive agent. Whether this unexpected in vitro effect is relevant in vivo, remains to be elucidated.
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