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Oleuropein, the Main Polyphenol of Olea europaea Leaf Extract, Has an Anti-Cancer Effect on Human BRAF Melanoma Cells and Potentiates the Cytotoxicity of Current Chemotherapies.

ABSTRACT: Oleuropein (Ole), a secoiridoid glucoside present in Olea europaea leaves, gained scientific interest thanks to its several biological properties, including the anticancer one. We verified whether Ole might potentiate the cytotoxicity of conventional drugs used to treat melanoma, disclosing a potentially new therapeutic strategy. We tested the cytotoxic action of Ole alone or in combination with chemotherapeutics on A375 human melanoma cells. We found that Ole was able, at a dose of 500 µM, to stimulate apoptosis, while at a non-toxic dose of 250 µM, it affected cell proliferation and induced the downregulation of the pAKT/pS6 pathway. A dose of 250 µM Ole did not potentiate the effect of Vemurafenib (PLX4032), but it succeeded in increasing the cytotoxic effect of Dacarbazine (DTIC). The major effect was found in the association between Ole and Everolimus (RAD001), also on PLX4032-resistant BRAF melanoma cells, which possibly cooperate in the inhibition of the pAKT/pS6 pathway. Of interest, an olive leaf extract enriched in equimolar Ole was more effective and able to further improve DTIC and RAD001 efficacy on BRAF melanoma cells with respect to Ole alone. Therefore, Ole represents a natural product able to potentiate a wide array of chemotherapeutics against BRAF melanoma cells affecting the pAKT/pS6 pathway.

SUBMITTER: Ruzzolini J

PROVIDER: S-EPMC6316801 | biostudies-other | 2018 Dec

REPOSITORIES: biostudies-other

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Olive Leaf Extract, from Olea europaea L., Reduces Palmitate-Induced Inflammation via Regulation of Murine Macrophages Polarization.

Project description:Olive tree (Olea europaea L.) leaves are an abundant source of bioactive compounds with several beneficial effects for human health. Recently, the effect of olive leaf extract in obesity has been studied. However, the molecular mechanism in preventing obesity-related inflammation has not been elucidated. Obesity is a state of chronic low-grade inflammation and is associated with an increase of pro-inflammatory M1 macrophages infiltration in the adipose tissue. In the current study, we explored Olea europaea L. leaf extract (OLE) anti-inflammatory activity using an in vitro model of obesity-induced inflammation obtained by stimulating murine macrophages RAW 264.7 with high dose of the free fatty acid palmitate. We found that OLE significantly suppressed the induction of pro-inflammatory mediators, tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β, nitric oxide (NO), prostaglandin E2 (PGE2) and reactive oxygen species (ROS), while it enhanced the anti-inflammatory cytokine, IL-10. Moreover, we demonstrated that OLE reduced the oxidative stress induced by palmitate in macrophages by regulating the NF-E2-related factor 2 (NRF2)-Kelch-like ECH-associated protein 1 (KEAP1) pathway. Finally, we showed that OLE promoted the shift of M1 macrophage toward less inflammatory M2-cells via the modulation of the associated NF-κB and proliferator-activated receptor gamma (PPARγ) signaling pathways. Thereby, our findings shed light on the potential therapeutic feature of OLE in recovering obesity-associated inflammation via regulating M1/M2 status.

| S-EPMC7761141 | biostudies-literature

Highly potent antioxidant Olea europaea L. leaf extract affects carotid and renal haemodynamics in experimental hypertension: The role of oleuropein.

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| S-EPMC5780626 | biostudies-literature

Extraction, Purification, and Characterization of Olive (<i>Olea europaea</i> L., cv. Chemlal) Polyphenol Oxidase.

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| S-EPMC10870767 | biostudies-literature

Olive (Olea europaea) leaf extract induces apoptosis and monocyte/macrophage differentiation in human chronic myelogenous leukemia K562 cells: insight into the underlying mechanism.

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| S-EPMC3997986 | biostudies-literature

In vitro Antifungal Activity of Olive (Olea europaea) Leaf Extracts Loaded in Chitosan Nanoparticles.

Project description:Olive leaf extract is characterized by a high content of phenols and flavonoids (oleuropein, luteolin, and their derivatives). These compounds are defined as secondary metabolites and exert such as anti-inflammatory, antioxidant, and antimicrobial activities. We investigated the in vitro antifungal activity of two olive leaf extracts (named EF1 and EF2) against a Fusarium proliferatum (AACC0215) strain that causes diseases to many economically important plants and synthesizing diverse mycotoxins. In this work, we aimed to identify the most appropriate concentration between the tested two olive leaf extracts to develop a safe, stable and efficient drug delivery system. Qualitative and quantitative analyses of the two olive leaf extracts by (HPLC) were performed. Furthermore, we also evaluated the antifungal effects of the two leaf extracts when encapsulated in chitosan-tripolyphosphate nanoparticles. The major compound in both EF1 and EF2 was oleuropein, with 336 and 603 mg/g, respectively, however, high concentrations of flavonoid were also present. EF1 and EF2 showed a concentration depended effect on F. proliferatum (AACC0215) viability. Our results showed a great efficacy of EF1/nanoparticles at the higher concentration tested (12X) against the target species. In this case, we observed an inhibition rate to both germination and growth of 87.96 and 58.13%, respectively. We suggest that EF1 olive leaf extracts, as free or encapsulated in chitosan-tripolyphosphate nanoparticles, could be used as fungicides to control plant diseases. Finally, future application of these findings may allow to reduce the dosage of fungicides potentially harmful to human health.

| S-EPMC7062645 | biostudies-literature

Phytochemical profile, cytotoxic, antioxidant, and allelopathic potentials of aqueous leaf extracts of Olea europaea

Project description:Abstract Although bioactivities of Olea europaea (OE) have been widely described, most of them were related to its methanolic extracts or its essential oils, While data related to aqueous extracts still very scarce. Thus, in this study, the phytochemical composition, the antioxidant activity, the cytotoxic potential, and the allelopathic potential of aqueous leaf extracts from two varieties of Olea europaea were investigated and compared. High?performance liquid chromatography (HPLC) was used to identify and quantify the constituents of the tested plants, and spectrophotometric methods to evaluate antioxidant activities. The cytotoxic potential was investigated using murine oligodendrocytes (158N) while germination seeds’ test was used for allelopathic activity. HPLC analysis showed the presence of 10 phenolic compounds in both extracts. Chemlali variety showed the highest antioxidant and allelopathic activities. Regarding the cytotoxicity effect, a significant increase in cell viability was observed with both of our extracts compared to untreated cells. These results confirm that aqueous extracts from OE produce a range of substances with potential antioxidant, antifungal, and allelopathic effects without toxic effects. Thus, they could be used as an alternative of chemical compounds. Data related to aqueous extracts are relatively rare. Thus, in this study, the phytochemical composition, the antioxidant activity, the cytotoxic potential, and the allelopathic potential of these extracts were investigated and compared.

| S-EPMC7500753 | biostudies-literature

Pan-erbB inhibition potentiates BRAF inhibitors for melanoma treatment.

Project description:The BRAF inhibitor vemurafenib is currently used for treating patients with BRAF V600E mutant melanoma. However, the responses to vemurafenib are generally partial and of relatively short duration. Recent evidence suggests that activation of the epidermal growth factor receptor (EGFR)/erbB signaling pathway may be responsible for the development of BRAF inhibitor resistance in melanoma patients. In this study, we characterized the erbB family of receptors and ligands in melanoma cell lines and examined whether targeting both BRAF and erbB provided enhanced antitumor activity in BRAF mutant melanoma. Variable levels of erbB2, erbB3, and truncated erbB4 were expressed in both BRAF wildtype and mutant melanoma cells with no significant differences between wildtype and mutant lines. EGFR was rarely expressed. Neuregulin 3 and neuregulin 4 were the major erbB ligands released by melanoma cells. Multi-erbB targeting with the irreversible tyrosine kinase inhibitor canertinib exerted a more effective growth inhibitory effect in both BRAF wildtype and mutant melanoma cells compared with the single-erbB or dual-erbB targeting inhibitors, gefitinib, erlotinib, and lapatinib. Canertinib inhibited both EGF-induced and neuregulin 1-induced erbB downstream signaling in both mutant and wildtype cell lines. However, canertinib induced apoptosis and sub-G1 arrest only in mutant cells. Canertinib statistically increased the antiproliferative effects of vemurafenib in the BRAF mutant melanoma cell lines while little or no enhanced effect was observed with the combination treatment in the wildtype cell lines. A combined inhibition strategy targeting BRAF together with multiple erbB family kinases is potentially beneficial for treating BRAF V600E mutant melanoma. Wildtype BRAF melanoma may also benefit from a multi-erbB kinase inhibitor.

| S-EPMC4394744 | biostudies-literature

Egyptian Olea europaea leaves bioactive extract: Antibacterial and wound healing activity in normal and diabetic rats.

Project description:Background and aimIn vitro activity evaluation of Egyptian Olea europaea leaves extracts, and in vivo healing activity assessment of the newly prepared ointment of Olea europaea leaves extracts mingled with Shea butter.Experimental procedureDifferent extraction methods and solvents were used to extract Egyptian Olea europaea bioactive agent(s). Antibacterial, scavenging activity and in-vivo evaluation of wound repair potentiality of Olea europaea extract were examined in normal and diabetic experimental rat models with induced circular excisions.Results and conclusionOlive leaves extract of Tanta was selected as the most active agent against Methicillin-resistant S. aureus (MRSA), with MIC value 15.6 μg/ml. Moreover, checkerboard dilution technique approved that the interaction between Tanta LEM crude extract and Ciprofloxacin was synergistic. Scavenging activity of the extract against DPPH free radicals was 87.55% at concentration of 50 μg/ml. In vivo normal and diabetic experimental rats treated with Shea butter: Tanta LEM extract (1:3 w/v) showed the maximum wound contraction and healing activity.

| S-EPMC8427474 | biostudies-literature

Proteome regulation during Olea europaea fruit development.

Project description:BackgroundWidespread in the Mediterranean basin, Olea europaea trees are gaining worldwide popularity for the nutritional and cancer-protective properties of the oil, mechanically extracted from ripe fruits. Fruit development is a physiological process with remarkable impact on the modulation of the biosynthesis of compounds affecting the quality of the drupes as well as the final composition of the olive oil. Proteomics offers the possibility to dig deeper into the major changes during fruit development, including the important phase of ripening, and to classify temporal patterns of protein accumulation occurring during these complex physiological processes.Methodology/principal findingsIn this work, we started monitoring the proteome variations associated with olive fruit development by using comparative proteomics coupled to mass spectrometry. Proteins extracted from drupes at three different developmental stages were separated on 2-DE and subjected to image analysis. 247 protein spots were revealed as differentially accumulated. Proteins were identified from a total of 121 spots and discussed in relation to olive drupe metabolic changes occurring during fruit development. In order to evaluate if changes observed at the protein level were consistent with changes of mRNAs, proteomic data produced in the present work were compared with transcriptomic data elaborated during previous studies.Conclusions/significanceThis study identifies a number of proteins responsible for quality traits of cv. Coratina, with particular regard to proteins associated to the metabolism of fatty acids, phenolic and aroma compounds. Proteins involved in fruit photosynthesis have been also identified and their pivotal contribution in oleogenesis has been discussed. To date, this study represents the first characterization of the olive fruit proteome during development, providing new insights into fruit metabolism and oil accumulation process.

| S-EPMC3547947 | biostudies-literature

An In Vitro and In Silico Study of the Enhanced Antiproliferative and Pro-Oxidant Potential of Olea europaea L. cv. Arbosana Leaf Extract via Elastic Nanovesicles (Spanlastics).

Project description:The olive tree is a venerable Mediterranean plant and often used in traditional medicine. The main aim of the present study was to evaluate the effect of Olea europaea L. cv. Arbosana leaf extract (OLE) and its encapsulation within a spanlastic dosage form on the improvement of its pro-oxidant and antiproliferative activity against HepG-2, MCF-7, and Caco-2 human cancer cell lines. The LC-HRESIMS-assisted metabolomic profile of OLE putatively annotated 20 major metabolites and showed considerable in vitro antiproliferative activity against HepG-2, MCF-7, and Caco-2 cell lines with IC50 values of 9.2 ± 0.8, 7.1 ± 0.9, and 6.5 ± 0.7 µg/mL, respectively. The encapsulation of OLE within a (spanlastic) nanocarrier system, using a spraying method and Span 40 and Tween 80 (4:1 molar ratio), was successfully carried out (size 41 ± 2.4 nm, zeta potential 13.6 ± 2.5, and EE 61.43 ± 2.03%). OLE showed enhanced thermal stability, and an improved in vitro antiproliferative effect against HepG-2, MCF-7, and Caco-2 (IC50 3.6 ± 0.2, 2.3 ± 0.1, and 1.8 ± 0.1 µg/mL, respectively) in comparison to the unprocessed extract. Both preparations were found to exhibit pro-oxidant potential inside the cancer cells, through the potential inhibitory activity of OLE against glutathione reductase and superoxide dismutase (IC50 1.18 ± 0.12 and 2.33 ± 0.19 µg/mL, respectively). These inhibitory activities were proposed via a comprehensive in silico study to be linked to the presence of certain compounds in OLE. Consequently, we assume that formulating such a herbal extract within a suitable nanocarrier would be a promising improvement of its therapeutic potential.

| S-EPMC8698813 | biostudies-literature

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