Format

Send to

Choose Destination
Mol Nutr Food Res. 2014 Mar;58(3):478-89. doi: 10.1002/mnfr.201300323. Epub 2013 Sep 9.

Oleuropein and hydroxytyrosol activate GPER/ GPR30-dependent pathways leading to apoptosis of ER-negative SKBR3 breast cancer cells.

Author information

1
Department of Pharmacy, Health and Nutrition Sciences, University of Calabria, Cosenza, Italy.

Abstract

SCOPE:

We have previously demonstrated that oleuropein (OL) and hydroxytyrosol (HT) reduce 17β-estradiol-mediated proliferation in MCF-7 breast cancer (BC) cells without affecting the classical genomic action of estrogen receptor (ER), but activating instead the ERK1/2 pathway. Here, we hypothesized that this inhibition could be mediated by a G-protein-coupled receptor named GPER/GPR30. Using the ER-negative and GPER-positive SKBR3 BC cells as experimental model, we investigated the effects of OL and HT on GPER-mediated activation of downstream pathways.

METHODS AND RESULTS:

Docking simulations and ligand-binding studies evidenced that OL and HT are able to bind GPER. MTT cell proliferation assays revealed that both phenols reduced SKBR3 cell growth; this effect was abolished silencing GPER. Focusing on OL and HT GPER-mediated pathways, using Western blot analysis we showed a sustained ERK1/2 activation triggering an intrinsic apoptotic pathway.

CONCLUSION:

Showing that OL and HT work as GPER inverse agonists in ER-negative and GPER-positive SKBR3 BC cells, we provide novel insights into the potential of these two molecules as tools in the therapy of this subtype of BC.

KEYWORDS:

Apoptosis; Breast cancer; GPER; Hydroxytyrosol; Oleuropein; SKBR3

PMID:
24019118
DOI:
10.1002/mnfr.201300323
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center