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Coffee polyphenols change the expression of STAT5B and ATF-2 modifying cyclin D1 levels in cancer cells
Carlota Oleaga1, Carlos J Ciudad, Véronique Noé
1Department of Biochemistry and Molecular Biology, School of Pharmacy, University of Barcelona, 08028 Barcelona, Spain.
Background:
Epidemiological studies suggest that coffee consumption reduces the risk of cancer, but the molecular mechanisms of its chemopreventive effects remain unknown.
Objective:
To identify differentially expressed genes upon incubation of HT29 colon cancer cells with instant caffeinated coffee (ICC) or caffeic acid (CA) using whole-genome microarrays.
Results:
ICC incubation of HT29 cells caused the overexpression of 57 genes and the underexpression of 161, while CA incubation induced the overexpression of 12 genes and the underexpression of 32. Using Venn-Diagrams, we built a list of five overexpressed genes and twelve underexpressed genes in common between the two experimental conditions. This list was used to generate a biological association network in which STAT5B and ATF-2 appeared as highly interconnected nodes. STAT5B overexpression was confirmed at the mRNA and protein levels. For ATF-2, the changes in mRNA levels were confirmed for both ICC and CA, whereas the decrease in protein levels was only observed in CA-treated cells. The levels of cyclin D1, a target gene for both STAT5B and ATF-2, were downregulated by CA in colon cancer cells and by ICC and CA in breast cancer cells.
Conclusions:
Coffee polyphenols are able to affect cyclin D1 expression in cancer cells through the modulation of STAT5B and ATF-2.
Insights
Coffee compounds like caffeic acid impact cancer cell gene expression, specifically downregulating cyclin D1 by influencing STAT5B and ATF-2 pathways. This reveals molecular mechanisms behind coffee's potential cancer-preventive properties.
Area of Science:
- Molecular Biology
- Genomics
- Cancer Research
Background:
- Epidemiological studies indicate coffee consumption may lower cancer risk.
- The precise molecular mechanisms underlying coffee's chemopreventive effects are not fully understood.
Purpose of the Study:
- To identify gene expression changes in HT29 colon cancer cells treated with instant caffeinated coffee (ICC) or caffeic acid (CA).
- To elucidate the molecular pathways involved in coffee's potential anti-cancer effects.
Main Methods:
- Whole-genome microarray analysis of HT29 cells incubated with ICC and CA.
- Venn-diagram analysis to identify common differentially expressed genes.
- Biological association network construction to pinpoint key regulatory nodes.
- Validation of gene and protein expression using quantitative methods.
Main Results:
- ICC and CA significantly altered gene expression in HT29 cells.
- STAT5B and ATF-2 emerged as key interconnected nodes in the gene regulatory network.
- STAT5B mRNA and protein levels were upregulated by ICC.
- ATF-2 mRNA levels changed with both ICC and CA, while protein levels decreased with CA.
- Cyclin D1, a downstream target, was downregulated by CA in colon cancer cells and by both ICC and CA in breast cancer cells.
Conclusions:
- Coffee polyphenols, including caffeic acid, modulate STAT5B and ATF-2.
- This modulation influences cyclin D1 expression in cancer cells.
- These findings provide insight into the molecular basis of coffee's chemopreventive potential.
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