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| Status |
Public on Jun 01, 2007 |
| Title |
Pathway and single gene analysis of Caco-2 cell differentiation by ascorbate-stabilized quercetin |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
The aim was to investigate mechanisms contributing to quercetin’s previously described effects on cell-proliferation and -differentiation, which contradicted its proposed anti-carcinogenic potency. In a 10-day experiment, 40 µM quercetin stabilized by 1mM 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 1,743 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 1,743 genes contributed to 27 affected pathways (P<0.05) categorized under 6 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 downregulated expression of genes involved in tumor-suppression and phase II metabolism, and upregulated 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 in the absence of 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.
Keywords: Colon cancer; Caco-2; quercetin; differentiation
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| Overall design |
Caco-2 cells were harvested on days 5 and 10 post-confluency. Per day, fold changes were calculated as quercetin vs. control.
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| Contributor(s) |
Dihal AA, Tilburgs C, van Erk MJ, Rietjens IM, Woutersen RA, Stierum RH |
| Citation(s) |
17639512 |
| Submission date |
Mar 13, 2007 |
| Last update date |
Dec 06, 2018 |
| Contact name |
Ashwin Dihal |
| E-mail(s) |
rob.stierum@tno.nl
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| Phone |
+31 (0)30-6944545
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| Fax |
+31 (0)30 6944989
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| Organization name |
TNO Quality of Life
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| Department |
Business Unit Physiologival Sciences
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| Street address |
Utrechtseweg 48
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| City |
Zeist |
| ZIP/Postal code |
3704 HE |
| Country |
Netherlands |
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| Platforms (1) |
| GPL571 |
[HG-U133A_2] Affymetrix Human Genome U133A 2.0 Array |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA98015 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE7259_RAW.tar |
14.6 Mb |
(http)(custom) |
TAR (of CEL, CHP) |
| Processed data provided as supplementary file |
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