Olive Oil‐derived Oleocanthal as Potent Inhibitor of Mammalian Target of Rapamycin: Biological Evaluation and Molecular Modeling Studies

Khanfar, Mohammad A.; Bardaweel, Sanaa K.; Akl, Mohamed R.; Sayed, Khalid A. El

doi:10.1002/ptr.5434

Cited by 56 publications

(72 citation statements)

References 46 publications

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“…Earlier studies indicated that (−)-oleocanthal is a potential inhibitor of the hepatocyte growth factor receptor (c-Met) pathway in breast cancer cells (Akl et al, 2014; Elnagar et al, 2011; Mohyeldin et al, 2016b). The antiproliferative effects of (−)-oleocanthal are mediated by inhibiting multiple c-Met downstream signaling molecules including protein kinase B (Akt), mitogen-activated protein kinase (MAPK), signal transducers and activators of transcription-3 (STAT-3), and mammalian target of rapamycin (mTOR) in multiple cancer cells (Akl et al, 2014; Fogli et al, 2016; Khanal et al, 2011; Khanfar et al, 2015; Pei et al, 2016; Scotece et al, 2013). In addition, (−)-oleocanthal induced cancer cell arrest by modulating the expression of cyclins, cyclin-dependent kinases, and arrest proteins (Akl et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

The olive oil phenolic (-)-oleocanthal modulates estrogen receptor expression in luminal breast cancer in vitro and in vivo and synergizes with tamoxifen treatment

Ayoub

Siddique

Ebrahim

et al. 2017

European Journal of Pharmacology

Self Cite

101

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Luminal breast cancer represents a therapeutic challenge in terms of aggressive disease and emerging resistance to targeted therapy. (−)-Oleocanthal has demonstrated anticancer activity in multiple human cancers. The goal of this study was to explore the effect of (−)-oleocanthal treatment on growth of luminal breast cancer cells and to examine the effect of combination of (−)-oleocanthal with tamoxifen. Results showed that (−)-oleocanthal inhibited growth of BT-474, MCF-7, and T-47D human breast cancer cells in mitogen-free media with IC50 values of 32.7, 24.07, and 80.93 μM, respectively. Similarly, (−)-oleocanthal suppressed growth of BT-474, MCF-7, and T-47D cells in 17β-estradiol-supplemented media with IC50 values of 22.28, 20.77, and 83.91 μM, respectively. Combined (−)-oleocanthal and tamoxifen treatments resulted in a synergistic growth inhibition of BT-474, MCF-7, and T-47D cells with combination index values of 0.65, 0.61, and 0.53 for each cell line, respectively. In-silico docking studies indicated high degree of overlapping for the binding of (−)-oleocanthal and 17β-estradiol to estrogen receptors, while (−)-oleocanthal and tamoxifen have distinguished binding modes. Treatment with 5 mg/kg or 10 mg/kg (−)-oleocanthal resulted in 97% inhibition of tumor growth in orthotopic athymic mice bearing BT-474 tumor xenografts compared to vehicle-treated animals. (−)-Oleocanthal treatment reduced total levels of estrogen receptors in BT-474 cells both in vitro and in vivo. Collectively, (−)-oleocanthal showed a potential beneficial effect in suppressing growth of hormone-dependent breast cancer and improving sensitivity to tamoxifen treatment. These findings provide rational for evaluating the effect of (−)-oleocanthal in combination with endocrine treatments in luminal breast cancer.

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Section: Discussionmentioning

confidence: 99%

The olive oil phenolic (-)-oleocanthal modulates estrogen receptor expression in luminal breast cancer in vitro and in vivo and synergizes with tamoxifen treatment

Ayoub

Siddique

Ebrahim

et al. 2017

European Journal of Pharmacology

Self Cite

101

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“…Particularly, the role of secoiridoids derived from Olea europaea L. has been investigated in different types of cancerous processes (Tables 1 and 2). OLE showed strong antiproliferative and downregulated the expression of phosphorylated mTOR [112] BT-474 [0-100 µ g/mL] OLE reduced breast cancer progression and locoregional recurrence models [113] MDA-MB-231 5 mg/mL OLE was able to control breast cancer progression [114] BT OLE showed strong antiproliferative and downregulated the expression of phosphorylated mTOR [112] BT-474 [0-100 µ g/mL] OLE reduced breast cancer progression and locoregional recurrence models [113] MDA-MB-231 5 mg/mL OLE was able to control breast cancer progression [114] BT OLE showed strong anti-proliferative and down-regulated the expression of phosphorylated mTOR [112] BT-474 [0-100 µg/mL] OLE reduced breast cancer progression and locoregional recurrence models [113] MDA-MB-231 5 mg/mL OLE was able to control breast cancer progression [114] BT-474 and MDA-MB-231…”

Section: Olive Tree Secoiridoids and Cancermentioning

confidence: 99%

“…The prevention of tumor recurrence was associated with the down-regulation of MET and HER 2 receptors and suppression of receptor activation [129]. OLE showed a strong anti-proliferative role against several breast cancer cell lines; for example, OLE was able to down-regulate the expression of phosphorylated mammalian target of rapamycin (mTOR) in metastatic MDA-BD-231 breast cancer cell lines [112] and inhibit the proliferation, migration, and invasion of the epithelial human breast cancer and prostate cancer cell lines (MCF7; MDA-BD-231; and PC3). In addition, LeGendre et al demonstrated that OLE selectively and rapidly induces cell death in cancer cells without being cytotoxic to noncancerous cells.…”

Section: Ol-aglyconementioning

confidence: 99%

Potential Protective Role Exerted by Secoiridoids from Olea europaea L. in Cancer, Cardiovascular, Neurodegenerative, Aging-Related, and Immunoinflammatory Diseases

et al. 2020

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Iridoids, which have beneficial health properties, include a wide group of cyclopentane [c] pyran monoterpenoids present in plants and insects. The cleavage of the cyclopentane ring leads to secoiridoids. Mainly, secoiridoids have shown a variety of pharmacological effects including anti-diabetic, antioxidant, anti-inflammatory, immunosuppressive, neuroprotective, anti-cancer, and anti-obesity, which increase the interest of studying these types of bioactive compounds in depth. Secoiridoids are thoroughly distributed in several families of plants such as Oleaceae, Valerianaceae, Gentianaceae and Pedialaceae, among others. Specifically, Olea europaea L. (Oleaceae) is rich in oleuropein (OL), dimethyl-OL, and ligstroside secoiridoids, and their hydrolysis derivatives are mostly OL-aglycone, oleocanthal (OLE), oleacein (OLA), elenolate, oleoside-11-methyl ester, elenoic acid, hydroxytyrosol (HTy), and tyrosol (Ty). These compounds have proved their efficacy in the management of diabetes, cardiovascular and neurodegenerative disorders, cancer, and viral and microbial infections. Particularly, the antioxidant, anti-inflammatory, and immunomodulatory properties of secoiridoids from the olive tree (Olea europaea L. (Oleaceae)) have been suggested as a potential application in a large number of inflammatory and reactive oxygen species (ROS)-mediated diseases. Thus, the purpose of this review is to summarize recent advances in the protective role of secoiridoids derived from the olive tree (preclinical studies and clinical trials) in diseases with an important pathogenic contribution of oxidative and peroxidative stress and damage, focusing on their plausible mechanisms of the action involved.

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“…Heat shock proteins though can interact with OC, so they are possible targets for cancer treatment [74]. Another way that OC can be used, as antitumor agent, is through targeting and downregulating mTOR, a protein that was found to participate in cancer, and especially to breast cancer, with the IC50 of OC to be in the range of nM [75].…”

Section: Oleocanthalmentioning

confidence: 99%

Olive Oil Phenols

Papanikolaou¹,

Melliou²,

Magiatis³

2019

Functional Foods

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Olive oils contain numerous substances that have a beneficial role in human health. Phenols are natural compounds that are present in extra-virgin olive oil (EVOO), and they are produced at the malaxation step of the olive oil production. The four most abundant phenols in EVOO are oleocanthal, oleacein, ligstroside aglycon, and oleuropein aglycon. These phenols exhibit significant biological effects in many diseases, participating in various cellular and biochemical processes. Oleocanthal can protect and prevent against the Alzheimer disease, demonstrates acute antiplatelet effects, which has a vital role against cancer, and can act like ibuprofen. Oleacein has antioxidant and anti-inflammatory activities and helps against atherosclerosis. Moreover, it acts as an antiaging factor and as a 5-lipoxygenase inhibitor. Ligstroside aglycon implicates to mechanisms against breast cancer, while oleuropein aglycon shows activities against the Alzheimer disease and breast cancer.

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Olive Oil‐derived Oleocanthal as Potent Inhibitor of Mammalian Target of Rapamycin: Biological Evaluation and Molecular Modeling Studies

Cited by 56 publications

References 46 publications

The olive oil phenolic (-)-oleocanthal modulates estrogen receptor expression in luminal breast cancer in vitro and in vivo and synergizes with tamoxifen treatment

The olive oil phenolic (-)-oleocanthal modulates estrogen receptor expression in luminal breast cancer in vitro and in vivo and synergizes with tamoxifen treatment

Potential Protective Role Exerted by Secoiridoids from Olea europaea L. in Cancer, Cardiovascular, Neurodegenerative, Aging-Related, and Immunoinflammatory Diseases

Olive Oil Phenols

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