Table 3.
Interaction of berry polyphenols with ER signaling
| Polyphenol | ER binding | Assay type | Effect | Dose | Cell type | Expression changes | Reference |
|---|---|---|---|---|---|---|---|
| Cyanidin | Y | Ligand binding; ERE-Luciferase | Antiestrogenic | MCF-7 | ↓ ERβ expression | (26, 137) | |
| Delphinidin | Y | Antiestogenic | ↓ ERα expression | ||||
| Pelargonidin | Y | Antiestrogenic | - | ||||
| Quercetin | Y (ERβ≫E Rα) | Estrogenic/Antiestrogenic | Biphasic effects | MCF-7 MDA-MB-231 |
↑ ER α and β mRNA | (21–22, 138) | |
| Kaempferol | Y (ERβ≫E Rα) | Ligand binding; Yeast transactivation | Estrogenic/Antiestrogenic | Biphasic effects | MCF-7 | ↓ ERα mRNA and protein ↓ PGR, Cyclin D1 and IRS-1 |
(21, 23, 139) |
| Resveratrol | Y (ERα > ERβ) | ERE-Luciferase | Estrogenic/Antiestrogenic | Biphasic effects | Ishikawa cells with stable ERs; MCF-7 |
↓ ERα by proteasomal degradation ↓ Cathepsin D and pS-2 Exhibits biphasic effects on EGFR-ER cross talk via dose-dependant induction of AKT |
(24, 140) |
| Ellagic Acid | Y | ERE-Luciferase | Estrogenic (via ERα)/Antiestrogenic (via ERβ) | HeLa | ↑ IGFBP3 levels similar to ICI 182,780 Co-treatment with ICI abrogates EA effect |
(27) | |
| Urolithin Aa | Y (ERα≫E Rβ) | Ligand binding assay | Antiestrogenic | MCF-7 | (28) | ||
| Urolithin Ba | Y (ERβ≫E Rα) | Antiestrogenic | |||||
| Enterolactonea | Y (ERα≫E Rβ) | ERE-Luciferase | Partial agonist | Ishikawa cells with stable ERs; MCF7; HeLa |
↑ ERβ ↓ E2-induced VEGF |
(24–25, 85) | |
Cell line origins: Breast -MCF-7(ER+), MDA-MB-231 (ER−); cervical-HeLa (ER−); endometrial-Ishikawa (ER−)
a
Urolithins A and B are gut metabolites of Ellagic acid and enterolactone is a gut metabolite of lignans.
ER- estrogen receptor; ERE- estrogen receptor response elements; PGR- progesterone receptor; IRS1- insulin receptor substrate 1; IGFBP3- insulin like growth factor binding protein-3; VEGF- vascular endothelial growth factors