Coffee Polyphenols Change the Expression of STAT5B and ATF-2 Modifying Cyclin D1 Levels in Cancer Cells

Abstract

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.

Soluble transferrin receptor and risk of type 2 diabetes in the obese and nonobese

“…These results suggest that obesity has an effect on sTfR homoeostasis that would explain the results in obese subjects found in the DPP cohort [7] and in our study. Meanwhile, coffee consumption has been related to an inhibition of the synthesis of sTfR [37], which is consistent with our findings. Alcohol consumption has been associated with higher body iron stores [36].…”

“…Elevated alcohol consumption and body iron stores may reduce cellular iron demands and, therefore, sTfR levels. Meanwhile, coffee consumption has been related to an inhibition of the synthesis of sTfR [37], which is consistent with our findings.…”

ATF7 is stabilized during mitosis in a CDK1-dependent manner and contributes to cyclin D1 expression

“…[35][36][37][38] Here, we demonstrate that interruption of either ATF7 or ATF2 loci decreases cyclin D1 protein expression to the same extends in two different cell lines. This strengthens the implication of ATF2 protein in targeting the cyclin D1 promoter [35][36][37]39 and highlights the contribution of ATF7 in such a mechanism.…”

Inhibition of Epstein-Barr virus reactivation by the flavonoid apigenin

“…Based on our finding, Zp inhibition by apigenin may be through interacting with Sp1/3, ATF-1/2 and CREB (Figure 6). After reviewing the literature, flavonoids have been found to have abilities to suppress Sp1 activity [48], interact with ATF-1/2 [49–51] and change the phosphorylation status of CREB [52]. From our results, we can postulate reasonably that apigenin inhibits Zp induction likely through a complex process, which may involve a combination of the Sp1/Sp3, ATF-1/2 and CREB pathways.…”