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To validate this hypothesis, we docked oleocanthal into the adenosine triphosphate binding pocket of a close mTOR protein homologue, namely, PI3K\u2010\u03b3. Apparently, oleocanthal shared nine out of ten critical binding interactions with a potent dual PIK3\u2010\u03b3\/mTOR natural inhibitor. Subsequent experimental validation indicated that oleocanthal indeed inhibited the enzymatic activity of mTOR with an IC<jats:sub>50<\/jats:sub> value of 708\u2009nM. Oleocanthal inhibits the growth of several breast cancer cell lines at low micromolar concentration in a dose\u2010dependent manner. Oleocanthal treatment caused a marked downregulation of phosphorylated mTOR in metastatic breast cancer cell line (MDA\u2010MB\u2010231). These results strongly indicate that mTOR inhibition is at least one of the factors of the reported anticancer and neuroprotective properties of oleocanthal. Copyright \u00a9 2015 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/ptr.5434","type":"journal-article","created":{"date-parts":[[2015,8,7]],"date-time":"2015-08-07T10:03:15Z","timestamp":1438941795000},"page":"1776-1782","source":"Crossref","is-referenced-by-count":58,"title":["Olive Oil\u2010derived Oleocanthal as Potent Inhibitor of Mammalian Target of Rapamycin: Biological Evaluation and Molecular Modeling Studies"],"prefix":"10.1002","volume":"29","author":[{"given":"Mohammad A.","family":"Khanfar","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, Faculty of Pharmacy The University of Jordan  Amman 11942 Jordan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanaa K.","family":"Bardaweel","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Faculty of Pharmacy The University of Jordan  Amman 11942 Jordan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohamed 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