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

被引:53
作者
Ayoub, Nehad M. [1 ]
Siddique, Abu Bakar [2 ]
Ebrahim, Hassan Y. [2 ]
Mohyeldin, Mohamed M. [2 ]
El Sayed, Khalid A. [2 ]
机构
[1] Jordan Univ Sci & Technol, Fac Pharm, Dept Clin Pharm, Irbid 22110, Jordan
[2] Univ Louisiana Monroe, Sch Pharm, Dept Basic Pharmaceut Sci, Monroe, LA 71201 USA
基金
美国国家卫生研究院;
关键词
(-)-Oleocanthal; Breast cancer; Luminal B; Estrogen receptor; 17; beta-estradiol; Tamoxifen; DRUG-COMBINATION; OLEOCANTHAL; MIP-1-ALPHA; INHIBITION; ANTAGONISM; KINASE; POTENT; MODEL; HER2;
D O I
10.1016/j.ejphar.2017.06.019
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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 IC50 values of 32.7, 24.07, and 80.93 mu M, respectively. Similarly, (-)-oleocanthal suppressed growth of BT-474, MCF-7, and T-47D cells in 17 beta-estradiol-supplemented media with IC50 values of 22.28, 20.77, and 83.91 mu M, 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 17 beta-estradiol to estrogen receptors, while (-)-oleocanthal and tamoxifen have distinguished binding modes. Treatment with 5 mg/kg or 10 mg/kg (-)-oleocanthal resulted in 97% inhibition of tumor growth in orthotbpic athymic mice bearing BT-474 tumor xenograffs 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.
引用
收藏
页码:100 / 111
页数:12
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