The olive oil phenolic (-)-oleocanthal modulates estrogen receptor expression in luminal breast cancer in vitro and in vivo and synergizes with tamoxifen treatment.

Autor: Ayoub NM; Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid 22110, Jordan. Electronic address: nmayoub@just.edu.jo., Siddique AB; Department of Basic Pharmaceutical Sciences, School of Pharmacy, University of Louisiana at Monroe, Monroe, LA 71201, USA., Ebrahim HY; Department of Basic Pharmaceutical Sciences, School of Pharmacy, University of Louisiana at Monroe, Monroe, LA 71201, USA., Mohyeldin MM; Department of Basic Pharmaceutical Sciences, School of Pharmacy, University of Louisiana at Monroe, Monroe, LA 71201, USA., El Sayed KA; Department of Basic Pharmaceutical Sciences, School of Pharmacy, University of Louisiana at Monroe, Monroe, LA 71201, USA.
Jazyk: angličtina
Zdroj: European journal of pharmacology [Eur J Pharmacol] 2017 Sep 05; Vol. 810, pp. 100-111. Date of Electronic Publication: 2017 Jun 15.
DOI: 10.1016/j.ejphar.2017.06.019
Abstrakt: Luminal breast cancer represents a therapeutic challenge in terms of aggressive disease and emerging resistance to targeted therapy. (-)-Oleocanthal has demonstrated anticancer activity in multiple human cancers. The goal of this study was to explore the effect of (-)-oleocanthal treatment on growth of luminal breast cancer cells and to examine the effect of combination of (-)-oleocanthal with tamoxifen. Results showed that (-)-oleocanthal inhibited growth of BT-474, MCF-7, and T-47D human breast cancer cells in mitogen-free media with IC 50 values of 32.7, 24.07, and 80.93µM, respectively. Similarly, (-)-oleocanthal suppressed growth of BT-474, MCF-7, and T-47D cells in 17β-estradiol-supplemented media with IC 50 values of 22.28, 20.77, and 83.91µM, respectively. Combined (-)-oleocanthal and tamoxifen treatments resulted in a synergistic growth inhibition of BT-474, MCF-7, and T-47D cells with combination index values of 0.65, 0.61, and 0.53 for each cell line, respectively. In-silico docking studies indicated high degree of overlapping for the binding of (-)-oleocanthal and 17β-estradiol to estrogen receptors, while (-)-oleocanthal and tamoxifen have distinguished binding modes. Treatment with 5mg/kg or 10mg/kg (-)-oleocanthal resulted in 97% inhibition of tumor growth in orthotopic athymic mice bearing BT-474 tumor xenografts compared to vehicle-treated animals. (-)-Oleocanthal treatment reduced total levels of estrogen receptors in BT-474 cells both in vitro and in vivo. Collectively, (-)-oleocanthal showed a potential beneficial effect in suppressing growth of hormone-dependent breast cancer and improving sensitivity to tamoxifen treatment. These findings provide rational for evaluating the effect of (-)-oleocanthal in combination with endocrine treatments in luminal breast cancer.
(Copyright © 2017 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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