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

A.A. Dihal, C. Tilburgs, M.J. van Erk, I.M.C.M. Rietjens, R.A. Woutersen, R.H. Stierum

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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.
Original languageEnglish
Pages (from-to)1031-1045
JournalMolecular Nutrition & Food Research
Volume51
Issue number8
DOIs
Publication statusPublished - 2007

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Keywords

  • metabolizing enzyme expression
  • surfactant-like particles
  • human colorectal-cancer
  • line caco-2
  • in-vitro
  • cells
  • flavonoids
  • proliferation
  • progression
  • profiles

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