Olive Oil-derived Oleocanthal as Potent Inhibitor of Mammalian Target of Rapamycin: Biological Evaluation and Molecular Modeling Studies
Khanfar MA, Bardaweel SK, Akl MR, El Sayed KA
Phytotherapy research : PTR · 51 citations
Review labels
Neutral facts our review recorded about how this study was done. They describe method, never whether we like the result.
How it was studied
- Design
- In vitro/mechanistic study (classified by our AI screen)
- Studied in
- Cells or lab samples
- Main outcome
- Mechanisms only
Who paid for it
- Funding
- Independent funding
- University or hospital
- Deanship of Scientific Research, University of Jordan
- Government
- National Cancer Institute
- Government
- NIH/NCI
- Government
- NCI NIH HHS
- University or hospital
- Deanship of Scientific Research at the University of Jordan
- Grants
- National Cancer Institute (1R15CA167475-01); National Cancer Institute (R15CA167475)
Based on 5 listed funder(s).
Publication
- Published
- 2015-08-07 · Phytother Res · vol. 29 · issue 11 · pp. 1776–1782
- Publisher
- Wiley
- Cited
- 61 citations · more than 87% of similar papers · 2.1× the field average
- References
- 48 works
- Access
- Open access (repository copy)
- Research areas
- PI3K/AKT/mTOR signaling in cancer · Synthesis and Biological Activity · Phytochemical Studies and Bioactivities
- Keywords
- PI3K/AKT/mTOR pathway, Neuroprotection, Pharmacology, Discovery and development of mTOR inhibitors, Chemistry, Downregulation and upregulation, Biochemistry, Biology, Signal transduction
- MeSH
- animals, humans, breast neoplasms, aldehydes, sirolimus, phenols, phosphorylation, models, molecular, female, phosphatidylinositol 3-kinases, tor serine-threonine kinases, olive oil, cyclopentane monoterpenes
4 authors
From JO, US
- Mohammad A. Khanfar · correspondingUniversity of Jordan
- Sanaa K. BardaweelUniversity of Jordan
- Mohamed R. AklUniversity of Louisiana at Monroe
- Khalid A. El SayedUniversity of Louisiana at Monroe
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.
Abstract via Europe PMC. Copyright remains with the authors or publisher.
Community trust
Loading…
How much do you trust this study's findings?
Comments
Sign in to rate, comment on or flag this study.Sign inSomething wrong here?
Flag this study if its information, labels or funding look wrong. An editor reviews every flag.
Sign in to rate, comment on or flag this study.Sign inEducational information about published research. Not medical advice, and not a recommendation to start or stop anything.