PMID- 26248874
OWN - NLM
STAT- MEDLINE
DCOM- 20160329
LR  - 20211203
IS  - 1099-1573 (Electronic)
IS  - 0951-418X (Print)
IS  - 0951-418X (Linking)
VI  - 29
IP  - 11
DP  - 2015 Nov
TI  - Olive Oil-derived Oleocanthal as Potent Inhibitor of Mammalian Target of 
      Rapamycin: Biological Evaluation and Molecular Modeling Studies.
PG  - 1776-82
LID - 10.1002/ptr.5434 [doi]
AB  - 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 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.
CI  - Copyright (c) 2015 John Wiley & Sons, Ltd.
FAU - Khanfar, Mohammad A
AU  - Khanfar MA
AD  - Department of Pharmaceutical Sciences, Faculty of Pharmacy, The University of 
      Jordan, Amman, 11942, Jordan.
FAU - Bardaweel, Sanaa K
AU  - Bardaweel SK
AD  - Department of Pharmaceutical Sciences, Faculty of Pharmacy, The University of 
      Jordan, Amman, 11942, Jordan.
FAU - Akl, Mohamed R
AU  - Akl MR
AD  - Department of Basic Pharmaceutical Sciences, School of Pharmacy, University of 
      Louisiana at Monroe, Monroe, Louisiana, USA.
FAU - El Sayed, Khalid A
AU  - El Sayed KA
AD  - Department of Basic Pharmaceutical Sciences, School of Pharmacy, University of 
      Louisiana at Monroe, Monroe, Louisiana, USA.
LA  - eng
GR  - R15 CA167475/CA/NCI NIH HHS/United States
GR  - 1R15CA167475-01/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20150807
PL  - England
TA  - Phytother Res
JT  - Phytotherapy research : PTR
JID - 8904486
RN  - 0 (Aldehydes)
RN  - 0 (Cyclopentane Monoterpenes)
RN  - 0 (Olive Oil)
RN  - 0 (Phenols)
RN  - AC7QO6038O (oleocanthal)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Aldehydes/*pharmacology
MH  - Animals
MH  - Breast Neoplasms/drug therapy/metabolism
MH  - Cyclopentane Monoterpenes
MH  - Female
MH  - Humans
MH  - *Models, Molecular
MH  - *Olive Oil
MH  - Phenols/*pharmacology
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Phosphorylation
MH  - Sirolimus
MH  - TOR Serine-Threonine Kinases/*antagonists & inhibitors
PMC - PMC5051273
MID - NIHMS791261
OTO - NOTNLM
OT  - antiproliferative
OT  - breast cancer
OT  - docking
OT  - mTOR
OT  - oleocanthal
COIS- The authors declare that there is no conflict of interest.
EDAT- 2015/08/08 06:00
MHDA- 2016/03/30 06:00
PMCR- 2016/10/05
CRDT- 2015/08/08 06:00
PHST- 2015/03/20 00:00 [received]
PHST- 2015/07/12 00:00 [revised]
PHST- 2015/07/21 00:00 [accepted]
PHST- 2015/08/08 06:00 [entrez]
PHST- 2015/08/08 06:00 [pubmed]
PHST- 2016/03/30 06:00 [medline]
PHST- 2016/10/05 00:00 [pmc-release]
AID - 10.1002/ptr.5434 [doi]
PST - ppublish
SO  - Phytother Res. 2015 Nov;29(11):1776-82. doi: 10.1002/ptr.5434. Epub 2015 Aug 7.