Figure 6.

The effect of polyphenols on nuclear ER, HER2 and IGF signaling pathways. Two main mechanisms of E2 action are depicted: (i) genomic activity of nuclear ER in connection with ERE or activating protein-1 (AP-1) transcription factors and (ii) cell surface activity of plasma membrane ER in connection with growth factor receptor signaling pathways [21,139]. Nuclear ER activity might be inhibited by genistein and resveratrol; the expression or phosphorylation of EGFR family can be downregulated by curcumin, resveratrol, quercetin and genistein; ERK phosphorylation can be reduced by curcumin; PI3K activity can be inhibited by EGCG and genistein, while Akt action can be inhibited by EGCG, genistein and apigenin [142,143,144,145,146,147,148,149]. Blue and red lines indicate stimulation and inhibition, respectively (for the sake of simplicity only the major proteins of the signaling pathways were included).