Coffee polyphenols change the expression of STAT5B and ATF-2 modifying cyclin D1 levels in cancer cells.
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.
Department of Biochemistry and Molecular Biology, School of Pharmacy, University of Barcelona, 08028 Barcelona, Spain.
Carlota
C
Oleaga
Carlos J
CJ
Ciudad
Véronique
V
Noé
Maria
M
Izquierdo-Pulido
D051698:Activating Transcription Factor 2 / Q000235:genetics* / Q000378:metabolism; D002109:Caffeic Acids / Q000494:pharmacology; D002110:Caffeine / Q000494:pharmacology; D045744:Cell Line, Tumor; D003069:Coffee / Q000737:chemistry*; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D053263:Gene Regulatory Networks / Q000187:drug effects / Q000235:genetics; D052138:Genes, Neoplasm / Q000235:genetics; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology; D059808:Polyphenols / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D050799:STAT5 Transcription Factor / Q000235:genetics* / Q000378:metabolism
C497105:ATF2 protein, human; D051698:Activating Transcription Factor 2; C530104:CCND1 protein, human; D002109:Caffeic Acids; D003069:Coffee; D059808:Polyphenols; D012333:RNA, Messenger; D050799:STAT5 Transcription Factor; C494095:STAT5B protein, human; D019938:Cyclin D1; D002110:Caffeine; C040048:caffeic acid