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Breast Cancer Research and Treatment
Erschienen in:

03.01.2021 | Preclinical study

Oleuropein is a natural inhibitor of PAI-1-mediated proliferation in human ER-/PR- breast cancer cells

verfasst von: Elena E. Tzekaki, George Geromichalos, Sophia N. Lavrentiadou, Maria P. Tsantarliotou, Anastasia A. Pantazaki, Angelos Papaspyropoulos

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 2/2021

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Abstract

Purpose

Elevated expression of PAI-1 has been widely linked with adverse outcomes in a variety of human cancers, such as breast, gastric and ovarian cancers, rendering PAI-1 a prognostic biomarker. As a result, several chemical inhibitors are currently being developed against PAI-1; however, the clinical setting where they might confer survival benefits has not yet been elucidated.

Methods

RNA sequencing data analysis from the TCGA/GTEx cancer portals (n = 3607 samples). In silico molecular docking analyses to predict functional macromolecule interactions. ER-/PR- (MDA-MB-231) and ER+/PR+ (MCF-7) breast cancer cell lines implemented to assess the effect of oleuropein as a natural inhibitor of PAI-1-mediated oncogenic proliferation.

Results

We show that high PAI-1 levels inversely correlate with ER and PR expressions in a wide panel of estrogen/progesterone-responsive human malignancies. By implementing an in silico molecular docking analysis, we identify oleuropein, a phenolic component of olive oil, as a potent PAI-1-binding molecule displaying increased affinity compared to the other olive oil constituents. We demonstrate that EVOO or oleuropein treatment alone may act as a natural PAI-1 inhibitor by incrementally destabilising PAI-1 levels selectively in ER-/PR- breast cancer cells, accompanied by downstream caspase activation and cell growth inhibition. In contrast, ER+/PR+ breast cancer cells, where PAI-1 expression is absent or low, do not adequately respond to treatment.

Conclusions

Our study demonstrates an inverse correlation between PAI-1 and ESR1/PGR levels, as well as overall patient survival in estrogen/progesterone-responsive human tumours. With a focus on breast cancer, our data identify oleuropein as a natural PAI-1 inhibitor and suggest that oleuropein-mediated PAI-1 destabilisation may confer clinical benefit only in ER-/PR- tumours.
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Metadaten
Titel
Oleuropein is a natural inhibitor of PAI-1-mediated proliferation in human ER-/PR- breast cancer cells
verfasst von
Elena E. Tzekaki
George Geromichalos
Sophia N. Lavrentiadou
Maria P. Tsantarliotou
Anastasia A. Pantazaki
Angelos Papaspyropoulos
Publikationsdatum
03.01.2021
Verlag
Springer US
Erschienen in
Breast Cancer Research and Treatment / Ausgabe 2/2021
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-020-06054-x

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