Journal
PHYTOTHERAPY RESEARCH
Volume 29, Issue 11, Pages 1776-1782Publisher
WILEY-BLACKWELL
DOI: 10.1002/ptr.5434
Keywords
oleocanthal; mTOR; breast cancer; docking; antiproliferative
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Funding
- Deanship of Scientific Research at the University of Jordan [1446]
- NIH/NCI [1R15CA167475-01]
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The established anticancer and neuroprotective properties of oleocanthal combined with the reported role of mammalian target of rapamycin (mTOR) in cancer and Alzheimer's disease development encouraged us to examine the possibility that oleocanthal inhibits mTOR. To validate this hypothesis, we docked oleocanthal into the adenosine triphosphate binding pocket of a close mTOR protein homologue, namely, PI3K-gamma. Apparently, oleocanthal shared nine out of ten critical binding interactions with a potent dual PIK3-gamma/mTOR natural inhibitor. Subsequent experimental validation indicated that oleocanthal indeed inhibited the enzymatic activity of mTOR with an IC50 value of 708nM. Oleocanthal inhibits the growth of several breast cancer cell lines at low micromolar concentration in a dose-dependent manner. Oleocanthal treatment caused a marked downregulation of phosphorylated mTOR in metastatic breast cancer cell line (MDA-MB-231). These results strongly indicate that mTOR inhibition is at least one of the factors of the reported anticancer and neuroprotective properties of oleocanthal. Copyright (C) 2015 John Wiley & Sons, Ltd.
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