ABSTRACT: We explored the anti-cancer capacity of (-)-oleocanthal in human hepatocellular carcinoma (HCC). (-)-Oleocanthal inhibited proliferation and cell cycle progression and induced apoptosis in HCC cells in vitro and suppressed tumor growth in an orthotopic HCC model. (-)-Oleocanthal also inhibited HCC cell migration and invasion in vitro and impeded HCC metastasis in an in vivo lung metastasis model. ( )-Oleocanthal acted by inhibiting epithelial-mesenchymal transition (EMT) through downregulation Twist, which is a direct target of STAT3. (-)-Oleocanthal also reduced STAT3 nuclear translocation and DNA binding activity, ultimately downregulating its downstream effectors, including the cell cycle protein Cyclin D1, the anti-apoptotic proteins Bcl-2 and survivin, and the invasion-related protein MMP 2. Overexpression of constitutively active STAT3 partly reversed the anti cancer effects of (-)-oleocanthal, which inhibited STAT3 activation by decreasing the activities of JAK1 and JAK2 and increasing the activity of SHP-1. These data suggest that (-)-oleocanthal may be a promising candidate for HCC treatment.·
Jun 2016 · Oncotarget
ABSTRACT: Numerous clinical and preclinical studies have suggested several health promoting effects for the dietary consumption of extra-virgin olive oil (EVOO) that could protect and decrease the risk of developing Alzheimer’s disease (AD). Moreover, recent studies have linked this protective effect to oleocanthal, a phenolic secoiridoid component of EVOO. This protective effect of oleocanthal against AD has been related to its ability to prevent amyloid-β (Aβ) and tau aggregation in vitro, and enhance Aβ clearance from the brains of wild type mice in vivo; however its effect in a mouse model of AD is not known. In the current study, we investigated the effect of oleocanthal on pathological hallmarks of AD in TgSwDI, an animal model of AD. Mice treatment for 4 weeks with oleocanthal significantly decreased amyloid load in the hippocampal parenchyma and microvessels. This reduction was associated with enhanced cerebral clearance of Aβ across the blood-brain barrier (BBB). Further mechanistic studies demonstrated oleocanthal to increase the expression of important amyloid clearance proteins at the BBB including P-glycoprotein and LRP1, and to activate the ApoE-dependent amyloid clearance pathway in the mice brains. The anti-inflammatory effect of oleocanthal in the brains of these mice was also obvious where it was able to reduce astrocytes activation and IL-1β levels. Finally, we could recapitulate the observed protective effect of oleocanthal in an in vitro human-based model, which could argue against species difference in response to oleocanthal. In conclusion, findings from in vivo and in vitro studies provide further support for the protective effect of oleocanthal against the progression of AD.
Sep 2015 · ACS Chemical Neuroscience
ABSTRACT: The Mediterranean countries have lower cancer incidence compared to the rest of European countries and the United States. Olive oil is a key ingredient of the Mediterranean diet. Olive oil secoiridoids have showed antiproliferative and apoptotic activity in HER2 overexpressing cancer cells. In addition, oleocanthal, a minor phenolic secoiridoid in extra-virgin olive oil, displays protective activity against inflammatory and Alzheimer’s disease. It has been shown that oleocanthal treatment inhibited the growth, migration, and invasion of human breast and prostate cancer cell lines. Oleocanthal was identified via a computer-assisted study as a c-Met activation inhibitor hit, targeting its ATP binding site, and stabilizing the kinase domain in its inactive conformation. It has been reported that oleocanthal competitively inhibited the phosphorylation of c-Met kinase in vitro in the Z’-LYTE assay, however, the exact antiproliferative, antimigratory, and pro-apoptotic mechanisms of oleocanthal are not well understood. In this study, the effects of oleocanthal on cell proliferation, migration and apoptosis in human breast cancer cells were evaluated. Oleocanthal treatment showed a dose-dependent inhibition of HGF-induced cell proliferation as shown by MTT, and Ki-67 immunostaining assay. Additional studies were conducted to determine the intracellular mechanisms mediating oleocanthal’s anticancer activity in breast cancer cells. Flow cytometry analysis showed that oleocanthal treatment increased the percentage of cells in G1 phase as compared to the vehicle-treated control group. Western blot studies revealed that blockade in cell cycle progression is associated with regulating the expression of various important G1/S modulators. Additional Western blot experiments showed that oleocanthal treatment caused a marked, dose-dependent decrease of HGF-induced c-Met receptor phosphorylation. Furthermore, oleocanthal treatment was associated with a relatively large suppression in HGF-induced of Erk1/2, Akt, PTK6 phosphorylation as compared to vehicle-treated control group. Additional studies were conducted to investigate whether the growth inhibitory effects of the oleocanthal treatment is associated with a concomitant activation of apoptotic pathways. Results of MTT assay showed that the oleocanthal treatment induced apoptosis at 25 µM. Activation of apoptosis by oleocanthal in MDA-MB-231 cells seemed to be initiated through induction of Fas ligand, which resulted in activation of caspase-8, caspase-3, and poly(ADPribose) polymerase(PARP). Additional studies showed that oleocanthal treatment inhibited HGF-induced migration of cancer cells, and suppressed HGF-induced epithelial-to-mesenchymal transition (EMT), as indicated by wound healing assay and a characteristic increased expression of epithelial cellular markers (E-cadherin, β-catenin) and a corresponding decrease in mesenchymal cellular markers (vimentin). These results suggest that oleocanthal is a promising hit with potential therapeutic use for the control of c-Met-dependent malignancies. This study was supported by the National Cancer Institute, grant number 1R15CA167475-01.
ABSTRACT: Oleocanthal is one of the phenolic compounds of extra virgin olive oil with important anti-inflammatory properties. Although its potential anticancer activity has been reported, only limited evidence has been provided in cutaneous malignant melanoma. The present study is aimed at investigating the selective in vitro antiproliferative activity of oleocanthal against human malignant melanoma cells. Since oleocanthal is not commercially available, it was obtained as a pure standard by direct extraction and purification from extra virgin olive oil. Cell viability experiments carried out by WST-1 assay demonstrated that oleocanthal had a remarkable and selective activity for human melanoma cells versus normal dermal fibroblasts with IC50s in the low micromolar range of concentrations. Such an effect was paralleled by a significant inhibition of ERK1/2 and AKT phosphorylation and downregulation of Bcl-2 expression. These findings may suggest that extra virgin olive oil phenolic extract enriched in oleocanthal deserves further investigation in skin cancer.
Jun 2016 · Nutrition and Cancer
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.
Aug 2015 · Phytotherapy Research
ABSTRACT: This review is a brief but comprehensive overview on the multi-target profile of oleocanthal, an extra-virgin olive oil (EVOO) phenol corresponding to the (-)-decarboxymethylligstroside aglycone, speculating about its potential in the prevention and/or treatment of various diseases, such as neurodegeneration, inflammation and cancer.
Dec 2015 · Current Bioactive Compounds
ABSTRACT: Extra virgin olive oil (EVOO) is consumed as part of the health promoting Mediterranean diet and contains several phenolic compounds that are responsible for the unique and distinctive flavour of EVOO. The phenolic fraction of EVOO also imparts many beneficial effects on human health. Oleocanthal is an EVOO phenolic that shares a unique perceptual quality with the non-steroidal anti-inflammatory drug (NSAID) ibuprofen and also mimics the anti-inflammatory actions of this drug. Oleocanthal has therefore been deemed a naturally occurring NSAID because of its demonstrated attenuation of cyclooxygenase (COX) activity in a dose dependent manner. New and emerging research has reported that oleocanthal also acts on inflammatory markers associated with neurodegenerative disease, joint degenerative disease, and cancer. This review will give an up-to-date summary of the history of oleocanthal and the current evidence establishing oleocanthal as a potent natural anti-inflammatory agent.
Oct 2012 · Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry – Anti-Inflammatory and Anti-Allergy Agents)
ABSTRACT: A new method for direct measurement of the oleocanthal and oleacein levels in olive oil by quantitative 1H-NMR was developed. The method was applied to the study of 175 monovarietal commercial Greek and Californian olive oil samples. The main findings were: 1. There was a significant variation concerning the concentrations of oleocanthal and oleacein among the studied samples. Their concentration ranged from non-detectable to 355 mg/Kg and their sum (index D1) from 0 to 501 mg/Kg. 2. There are olive varieties that independently of geographic origin and harvest time produce oil that contains both compounds in low levels 3. There is positive correlation of high level of oleocanthal and oleacein in olive oils with the early time of harvest. Although there is need for more extensive study, a new index for the characterization of extra virgin olive oils which is a combination of D1= oleocanthal+oleacein level and D2=oleocanthal/oleacein ratio seems to be very useful.
Nov 2012 · Journal of Agricultural and Food Chemistry
ABSTRACT: Extra-virgin olive oil (EVOO), a principal component of the Mediterranean diet (Med diet), is one of the most ancient known foods and has long been associated with health benefits. Many phenolic compounds extracted from Olea europea L. have attracted attention since their discovery. Among these phenolic constituents, oleocanthal has recently emerged as a potential therapeutic molecule for different diseases, showing relevant pharmacological properties in various pathogenic processes, including inflammation, cancers and neurodegenerative diseases. Here, we discuss and summarize the most recent pharmacological evidence for the medical relevance of oleocanthal, focusing our attention on its anti-inflammatory and chemotherapeutic roles.
Nov 2014 · Drug Discovery Today
ABSTRACT: Abstract Introduction : The main components of olive oil include oleic acid, phenolics compounds (hydroxytyrosol, tyrosol, and oleuropein) and squalene. Studies have demonstrated that the phenolic compounds of olive oil have positive effects on certain physiological parameters, such as plasma lipoproteins, oxidative damage, inflammatory markers, platelet and cellular function and antimicrobial activity. This study aimed to review studies on the health benefits of olive oil. Related articles in English were searched in Pubmed, Science direct, Google scholar, Springer, Wiley Online Library and Elsevier in human, animal, in vitro and in vivo studies. Results showed a lower incidence of coronary heart disease (by antithrombotic properties and improving lipid profiles, vascular function, blood pressure and oxidative stress) and certain cancers (mainly breast, colorectal and prostate cancers). Olive oil was found to lead to modification of immune and inflammatory responses. Oleocanthal, a phenolic compound in virgin olive oil, has possesses anti- inflammatory properties similar to ibuprofen. Olive oil also appears to have a role in bone mineralization. In studies on rats, tyrisol, hydroxytyrosol and oleuropein significantly increased bone formation and can hence be used as effective remedies in the treatment of osteoporosis symptoms. The beneficial effects of olive oil are attributed to its monounsaturated fatty acids (MUFA) and phenolic compounds.
Jul 2015 · Iranian Journal of Endocrinology and Metabolism
ABSTRACT: Amyloid diseases are characterized by the deposition of typically aggregated proteins/peptides in tissues, associated with degeneration and progressive functional impairment. Alzheimer’s disease is one of the most studied neurodegenerative amyloid diseases and, in Western countries, a significant cause of dementia in the elderly. The so-called “Mediterranean diet” has been considered for long as the healthier dietary regimen, characterised by a great abundance in vegetables and fruits, extra virgin olive oil as the main source of fat, a moderate consumption of red wine and a reduced intake of proteins from red meat. Recent epidemiological studies support the efficacy of the Mediterranean diet not only against cardiovascular and cancer diseases (as previously demonstrated) but also against the cognitive decline associated with ageing, and several data are highlighting the role played by natural phenols, of which red wine and extra virgin olive oil are rich, in such context. In the meantime, studies conducted both in vivo and in vitro have started to reveal the great potential of the phenolic component of extra virgin olive oil (mainly oleuropein aglycone and oleocanthal) in counteracting amyloid aggregation and toxicity, with a particular emphasis on the pathways involved in the onset and progression of Alzheimer’s disease: amyloid precursor protein processing, amyloid-beta (Aβ) peptide and tau aggregation, autophagy impairment, neuroinflammation. The aim of this review is to summarize the results of such research efforts, showing how the action of these phenols goes far beyond their renowned antioxidant activity and revealing their potential as multi-targeting agents against Alzheimer’s disease.
Jun 2015 · Advances in Experimental Medicine and Biology
ABSTRACT: Adherence to the Mediterranean Diet (MD) has been associated with a reduced incidence of neurodegenerative diseases and better cognitive performance. Virgin olive oil, the main source of lipids in the MD, is rich in minor phenolic components, particularly hydroxytyrosol (HT). HT potent antioxidant and anti-inflammatory actions have attracted researchers’ attention and may contribute to neuroprotective effects credited to MD. In this review HT bioavailability and pharmacokinetics are presented prior to discussing health beneficial effects. In vitro and in vivo neuroprotective effects together with its multiple mechanisms of action are reviewed. Other microconstituents of olive oil are also considered due to their potential neuroprotective effects (oleocanthal, triterpenic acids). Finally, we discuss the potential role of HT as a therapeutic tool in the prevention of neurodegenerative diseases.
Mar 2015 · Molecules
ABSTRACT: The health benefits of the Mediterranean Diet can be largely ascribed to the nutraceutical properties of extra-virgin olive oil (EVOO). Monounsaturated fatty acids and various phenolic compounds such as oleocanthal, oleuropein, hydroxytyrosol and tyrosol are the main nutraceutical substances of EVOO. These substances have been suggested to have the ability to modulate ageing- associated processes. In experimental models, it was shown that EVOO with high concentration of poliphenols has anti-inflammatory and antioxidant properties. Indeed, it was observed that hydroxytyrosol, as well as oleocanthal, inhibit the cyclooxygenases (COX-1 and 2), responsible for prostaglandin production; oleuropein is a radical scavenger that blocks the low-density lipoproteins oxidation. Due to the relevance of the olive oil in the economy of Sicily, our group has been funded to assess the nutraceutical properties of different kinds of olive oil. Indeed, the aim of the study is to evaluate effects of EVOOs, with low and high polyphenols content, on the immuno- inflammatory and oxidative stress responses in young and old people. Further objective of our group is to evaluate effects of EVOO, with low and high polyphenols content, on the expression of genes encoding proteins that take part in Insulin/Insulin-like growth factor-1 signaling pathway involved in longevity. The results of the study will be useful to produce olive oil enriched in nutraceutical properties, likely helpful in the prevention of age-related diseases.
Nov 2013 · Rejuvenation Research
ABSTRACT: Multiple myeloma (MM) is a plasma cell malignancy that causes devastating bone destruction by activating osteoclasts in the bone marrow milieu. MM is the second of all hematological malignancies. Thus, the search for new pharmacological weapons is under intensive investigation being MM a critically important public health goal. Recently, it has been demonstrated that macrophage inflammatory protein 1- alpha (MIP-1α) is crucially involved in the development of osteolytic bone lesions in MM. Phenolic components of extra virgin olive oil are reported to have anti tumor activity. However, the underlying mechanisms and specific targets of extra virgin olive oil remain to be elucidated. In the present study, we investigated the effects of a recently isolated novel extra virgin olive oil polyphenol, oleocanthal, on the human multiple myeloma cell line ARH-77. Here we report that this natural compound has a remarkable in vitro activity by inhibiting MIP-1α expression and secretion in MM cells. In addition, we also demonstrated that oleocanthal inhibits MM cells proliferation by inducing the activation of apoptosis mechanisms and by down-regulating ERK1/2 and AKT signal transduction pathways.
Mar 2013 · Current Medicinal Chemistry
ABSTRACT: The beneficial role of extra-virgin olive oil on human health has recently been attributed to the presence of minor components, with a particular interest in phenolic compounds. The phenolic composition of olive oil is complex and includes hydroxytyrosol (3,4-dihydroxyphenylethanol: HT), tyrosol (hydroxyphenylethanol), the dialdehydic form of elenolic acid linked to hydroxytyrosol or tyrosol (oleocanthal), oleuropein aglycon and lignans. Olive oil phenols, in particular HT, have been carefully studied over the last few years and it appears that this phenol could help to prevent chronic-degenerative diseases such as cardiovascular diseases and cancer due to its antioxidant faculties. However, the biological effects of olive oil polyphenols are not limited to their antioxidant ability. Indeed, several researchers have recently demonstrated that olive oil polyphenols are also able to modulate both gene expression and various pathways involved in the regulation of many physiological and pathological conditions. This study illustrates our recent findings on the in-vitro chemo-preventive activities of HT. We have demonstrated that HT, at relatively high doses (100μM), is able to inhibit proliferation and to arrest cell cycle progression through the up-regulation of the cyclin-dependent, protein-kinase inhibitors p21 and p27 on HL60 promyelocytic cell line. These effects were associated to the induction of differentiation and apoptosis. The initial stress signal responsible for these effects was the HT-induced extracellular production of H2O2. HT was also able to inhibit the proliferation of human tumour cells from the colon, prostate and breast, indicating its important role in the prevention of the promotion phase of carcinogenesis. Moreover, we have observed through the comet assay that at lower doses (1-10μM) HT is able to inhibit the oxidative DNA damage in human leukocytes thus suggesting a preventive mechanism in the initiation phase of carcinogenesis. These results underline that HT is able to induce either pro-oxidant or anti-oxidant effects which depend on exposition doses. Furthermore, we demonstrated that HT (50-100μM) was able to prevent LPS-mediated COX2 induction on human monocytes at both mRNA and protein levels. These effects were associated with a significant reduction of PGE2 accumulation in the culture medium. Moreover, in the same experimental conditions HT increased the release of TNFa by monocytes. All together, our in-vitro data supports the hypothesis that olive oil phenols may be an important element in the cancer prevention properties of the Mediterranean diet.
ABSTRACT: Background and Objective: Virgin Olive oil contains Oleocanthal as an anti-inflammatory agent. The main purpose of this study was to compare the effects of ultrasound therapy and phonophoresis with virgin olive oil on female athletes’ chronic Low Back Pain (LBP). Materials and Methods: Thirty female athletes with chronic LBP voluntarily participated in this pilot study. Patients were randomly assigned to Phonophoresis (n=15) and Ultrasound (n=15) groups and were treated with virgin olive oil or ultrasound gel for 10 sessions. Frequency and duration of treatment by ultrasound were 1 MHz and 10-min, respectively. Subjects completed Mc Gill, Modified Oswestry and Ronald-Morris standard questionnaires before and after 10 sessions of physiotherapy. Results: There was a significant reduction in symptoms of LBP based on Mc Gill, Ronald-Morris, and Modified Oswestry questionnaires at the end of the therapy in both groups compared to pre-treatment status (P<0.05). Although the mean post-treatment scores were lower than the mean pre-treatment scores in all questionnaires in phonophoresis compared with ultrasound group, there was no significant difference in symptoms of LBP between two groups (P>0.05). Conclusion: It seems both ultrasound and phonophoresis with virgin olive oil are effective methods for treatment of chronic LBP in female athletes.
Jan 2014 · Journal of Zanjan University of Medical Sciences and Health Services
ABSTRACT: Background: Oleacein (dialdehydic form of decarboxymethyl elenolic acid linked to hydroxytyrosol; 3,4-DHPEA-EDA) have been proven to possess antioxidant and anti-inflammatory activity. Purpose: In this study, we examined whether oleacein could increase CD163 and IL-10 receptor expression as well as HO-1 intracellular secretion in human macrophages. Methods: Effect of oleacein (10 and 20 μmol/l) or oleacein together with complexes of haemoglobin (Hb) and haptoglobin 1-1 (Hp11) or haptoglobin 2-2 (Hp22) on expression of IL-10 and CD163 receptor was determined by Flow Cytometry. Expression of CD163mRNA was measured by real-time quantitative RT-PCR. Heme oxygenase 1 (HO-1) intracellular secretion in macrophages was investigated by enzyme-linked immunosorbent assay (ELISA). Results: Oleacein (OC) together with complexes HbHp11 or HbHp22 stimulated the expression of CD163 (30-100-fold), IL-10 (170-300-fold) and HO-1 secretion (60-130-fold) after 5 days of coincubation. The 2-fold (24 h), 4-fold (48 h) increase of CD163 mRNA level and its final (72 h) decrease was also observed. Conclusion: Our results suggested that oleacein enhances anti-inflammatory activity of complexes haemoglobin with haptoglobin 1-1 and 2-2 and could play a potential role in the prevention of inflammatory disease related to atherosclerosis.
Nov 2015 · Phytomedicine: international journal of phytotherapy and phytopharmacology
ABSTRACT: Polyphenols, such as oleacein (3,4-DHPEA-EDA; 3,4-dihydroxyphenylethanol-elenolic acid dialdehyde), are believed to play a role in the prevention of cardiovascular diseases. Due to an increase of neutrophil mediators in acute myocardial infarction the aim of this study was to establish the effect of oleacein on neutral endopeptidase (NEP) activity and other functions of human neutrophils, such as elastase, MMP-9 and IL-8 production. The effect on CD62L and CD11b/CD18 expression on neutrophils was also determined. Oleacein with a concentration of 100 μM inhibited NEP activity, elastase, MMP-9 and IL-8 release from neutrophils by 77.7 ± 2.7%, 21.3 ± 7.8%, 22.7 ± 4.2% and 25.2 ± 5.6%, respectively. Oleacein with a concentration of 50 μM suppressed CD11b/CD18 expression by 63.6 ± 3.1% and to a lesser extent, increased CD62L expression by 27.3 ± 8.3% on the surface of neutrophils, in comparison with stimulated cells. Oleacein by inhibiting NEP activity, adhesion molecules expression and elastase release might play a role in the protective effects of olive oil against endothelial injuries.
Jun 2014 · Food Chemistry
ABSTRACT: Endothelial progenitor cells (EPCs) are responsible for neovascularization of ischaemic tissue and may participate in re-endothelization of an injured arterial wall. There is evidence that angiotensin II, by an increase of gp91phox expression and induction of ROS generation, accelerates cell senescence and impairs functions of EPCs. Oleacein is a main phenolic compound from olive oil, whereas oleuropein is present in olive leaves. Both compounds possess antioxidative, hypotensive and anti-inflammatory properties and show beneficial activity on the cardiovascular system. In this study, we examined whether oleoeuropein and oleacein could protect EPCs against impairment of their functions due to angiotensin-induced cell senescence. CD31(+)/VEGFR-2(+) cells were isolated from young healthy volunteers blood samples and cultured on fibronectin-coated plates with angiotensin (1.0μM) in presence or absence of increasing concentrations (from 1.0 to 10.0μM) of oleoeuropein or oleacein. As compared to angiotensin II-treated cells, EPCs exposed to oleacein or oleuropein prior to angiotensin II showed a significant increase of proliferation and telomerase activity, and a decrease in the percentage of senescent cells and intracellular ROS formation. Oleacein and oleuropein restored migration, adhesion and tube formation of EPCs diminished by angiotensin II in a concentration-dependent manner. This effect was related to NF-E2-related factor 2 (Nrf2) transcription factor activation and the increase of heme oxygenase-1 (HO-1) expression.
Jun 2013 · Phytomedicine: international journal of phytotherapy and phytopharmacology
ABSTRACT: Epidemiological studies suggest that the cardioprotective properties of olive oil, particularly extra-virgin type, result from a positive influence of its components, such as phenolic compounds, on the cardiovascular system. One of the most abundant phenolic compounds of extra virgin olive oil is the dialdehydic form of elenolic acid conjugated with 3, 4-(dihydroxyphenyl)ethanol (3, 4-DHPEA-EDA), also known as oleacein. Due to its abundance in olive oil, it may play a special role in decreasing the progression of atherosclerosis. Some bioactivities of oleacein, such as antioxidant, anti-inflammatory, anti-proliferative and antimicrobial, were documented. There is also evidence of the bioavailability of oleacein in humans as well. However, due to the lack of clinical data, further studies are needed to provide further information about the usefulness of this compound in antiatherosclerotic therapy.
Oct 2014 · Current Pharmaceutical Design
ABSTRACT: Oleocanthal is a bioactive compound from olive oil. It has attracted considerable attention as it is anti-inflammatory, antiproliferative, and has been shown to possess neuroprotective properties in vitro and in vivo. Delineated from its polyphenolic structure, the aim of this study was to characterize oleocanthal towards estrogenic properties. This might contribute to partly explain the beneficial effects described for the Mediterranean diet. Estrogenic properties of oleocanthal were assessed by different methods: a) stimulation of reporter gene activity in MVLN or RNDA cells either expressing estrogen receptor α or β, b) stimulation of luciferase reporter gene activity in U2OS osteosarcoma cells expressing estrogen receptor α or β, and c) elucidation of the impact on estradiol-induced gene expression in U2OS cells transduced with both estrogen receptors. Depending on the cell line origin, oleocanthal inhibited luciferase activity (MVLN, U2OS-estrogen receptor β) or weakly induced reporter gene activity at 10 µM in U2OS-estrogen receptor α cells. However, oleocanthal inhibited stimulation of luciferase activity by estradiol from both estrogen receptors. Oleocanthal, if given alone, did not stimulate gene expression in U2OS cells, but it significantly modulated the response of estradiol. Oleocanthal enhanced the effect of estradiol on the regulation of those genes, which are believed to be regulated through heterodimeric estrogen receptors. As the estrogenic response pattern of oleocanthal is rather unique, we compared the results obtained with oleacein. Oleocanthal binds to both estrogen receptors inducing estradiol-agonistic or antiagonistic effects depending on the cell line. Regarding regulation of gene expression in U2OS-estrogen receptor α/β cells, oleocanthal and oleacein enhanced estradiol-mediated regulation of heterodimer-regulated genes.
Jul 2015 · Planta Medica