Table 1.
Summary of known effects of dietary polyphenols on cancer hallmarks through estrogen receptor subtype (ERα or ERβ)-mediated molecular mechanisms.
| Polyphenol Compounds | ERα | ERα-Dependent Functions | ERβ | ERβ-Dependent Functions | References |
|---|---|---|---|---|---|
| Naringenin Quercetin | Antagonize ERα rapid signaling, inducing the persistent activation of p38, the inhibition of AKT and ERK1/2 E2-dependent activation. No effect on ERα transcriptional mechanism. | Inhibit proliferation in ERα-expressing cancer cells and induce pro-apoptotic cascade. Impair the E2-dependent upregulation of Ngb and sensitize breast cancer cells to apoptotic effect of paclitaxel. |
Mimic E2 effect activating p38/MAPK pathway | Induction of ERβ mediated pro-apoptotic pathway | [52,114,127,128,129,130] |
| Genistein | Agonistic effect. Trans-activation of ERα inducing the persistent activation of ERK1/2. |
Induction of MCF-7 cell proliferation in vitro and implanted in xenograft mice; stimulation of E2-dependent mammary tumors’growth. Inhibits cell growth and induces apoptosis in long-term estrogen deprived MCF7 |
E2 mimetic effects. Suppression of the ERK1/2, PI3K/AKT activation and PCNA and NFkB expression. Downregulation of migration-related pathways such as the FAK, PI3K/AKT and TGFβ pathways. |
Suppression of cancer cell growth. Inhibition of migration in ovarian and prostate cancer cells and reduction of cancer metastasis in colorectal cancer. |
[118,119,125,131,132,133] |
| Daidzein Equol | Agonist | Induce in vitro MCF-7 cell proliferation Increase lung metastasis in in vivo model of breast cancer. | Agonist | Inhibit cancer cells proliferation. Suppress ovarian cancer cell migration. | [125,126,134,135,136] |
| Resveratrol | Full antagonist of ERα rapid and transcriptional mechanisms | Induce pro-apoptotic effects reducing the Bcl-2/BAX ratio. Downregulates Ngb intracellular content and sensitizes breast cancer cells to the paclitaxel pro-apoptotic effect. | Agonist | Increases Ngb levels and cell-survival in neuron-derived cells | [55,128] |
| Kaempferol | Antagonist | Suppresses EMT transition and metastic behavior of MCF-7 induced by endogenous E2 or estrogen mimetic compounds. | ND | ND | [137] |
EMT. Epithelial–mesenchymal transition; Ngb. Neuroglobin. For further elucidation see the text.