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

Adele Chimento, Ivan Casaburi, Camillo Rosano, Paola Avena, Arianna De Luca, Carmela Campana, Emilia Martire, Maria Francesca Santolla, Marcello Maggiolini, Vincenzo Pezzi, Rosa Sirianni

Research output: Contribution to journalArticle

58 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)478-489
Number of pages12
JournalMolecular Nutrition and Food Research
Volume58
Issue number3
DOIs
StatePublished - Mar 1 2014

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Keywords

  • Apoptosis
  • Breast cancer
  • GPER
  • Hydroxytyrosol
  • Oleuropein
  • SKBR3

ASJC Scopus subject areas

  • Biotechnology
  • Food Science

Cite this

Chimento, A., Casaburi, I., Rosano, C., Avena, P., De Luca, A., Campana, C., Martire, E., Santolla, M. F., Maggiolini, M., Pezzi, V., & Sirianni, R. (2014). Oleuropein and hydroxytyrosol activate GPER/ GPR30-dependent pathways leading to apoptosis of ER-negative SKBR3 breast cancer cells. Molecular Nutrition and Food Research, 58(3), 478-489. https://doi.org/10.1002/mnfr.201300323