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
| Jazyk: | angličtina |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
cell division
drug effect article colon tumor DNA microarray Gene Expression Caco-2 Cell Differentiation Ascorbic Acid Microarray Colorectal cancer quercetin Drug Stability Toxicology and Applied Pharmacology cell strain CACO 2 Differentiation Colonic Neoplasms Humans pathology genetics human Caco-2 Cells comparative study Oligonucleotide Array Sequence Analysis |
| Popis: | 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 μM quercetin stabilized by 1 mM ascorbate reduced Caco-2 differentiation up to 50% (p < 0.001). Caco-2 RNA from days 5 and 10, hybridized on HG-U133A2.0 Affymetrix GeneChips®, 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 II metabolism, and up-regulated oncogenes. Gene expression changes mediated by ascorbate-stabilized quercetin were concordant with those occurring in human colorectal carcinogenesis (≈80-90%), but were opposite to those previously described for Caco-2 cells exposed to quercetin without ascorbate (≈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. © 2007 WILEY-VCH Verlag GmbH & Co. KGaA. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|