title: Olive Oil-derived Oleocanthal as Potent Inhibitor of Mammalian Target of Rapamycin: Biological Evaluation and Molecular Modeling Studies.
abstract: 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-γ. Apparently, oleocanthal shared nine out of ten critical binding interactions with a potent dual PIK3-γ/mTOR natural inhibitor. Subsequent experimental validation indicated that oleocanthal indeed inhibited the enzymatic activity of mTOR with an IC50 value of 708 nM. 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.
authors.affiliation: Department of Pharmaceutical Sciences, Faculty of Pharmacy, The University of Jordan, Amman, 11942, Jordan.
authors.forename: Mohammad A
authors.initials: MA
authors.lastname: Khanfar
authors.affiliation: Department of Pharmaceutical Sciences, Faculty of Pharmacy, The University of Jordan, Amman, 11942, Jordan.
authors.forename: Sanaa K
authors.initials: SK
authors.lastname: Bardaweel
authors.affiliation: Department of Basic Pharmaceutical Sciences, School of Pharmacy, University of Louisiana at Monroe, Monroe, Louisiana, USA.
authors.forename: Mohamed R
authors.initials: MR
authors.lastname: Akl
authors.affiliation: Department of Basic Pharmaceutical Sciences, School of Pharmacy, University of Louisiana at Monroe, Monroe, Louisiana, USA.
authors.forename: Khalid A
authors.initials: KA
authors.lastname: El Sayed
mesh_terms: D000447:Aldehydes / Q000494:pharmacology*; D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism; D000081004:Cyclopentane Monoterpenes; D005260:Female; D006801:Humans; D008958:Models, Molecular; D000069463:Olive Oil; D010636:Phenols / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D020123:Sirolimus; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*
chemical_list: D000447:Aldehydes; D000081004:Cyclopentane Monoterpenes; D000069463:Olive Oil; D010636:Phenols; D019869:Phosphatidylinositol 3-Kinases; D020123:Sirolimus; D058570:TOR Serine-Threonine Kinases; C503534:oleocanthal; C546842:MTOR protein, human
keywords: antiproliferative; breast cancer; docking; mTOR; oleocanthal