Oleuropein induces apoptosis in colorectal tumor spheres via mitochondrial fission
Da Yeon KimSangmi ParkJisoo YunWoongbi JangVinoth Kumar RethineswaranLe Thi Hong VanLy Thanh Truong GiangJaewoo ChoiHye Ji LimSang‐Mo Kwon
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Viability assay
Oleuropein
Abstract Oleuropein is one of the two main phenolic compounds derived from olive leaves. Numerous studies have found that the polyphenols contained in olive leaves possess strong antioxidant properties, and increase apoptosis in many types of cancer cells, suggesting its possible efficacy as an anti-cancer treatments. The purpose of our study was to examine the effects of oleuropein extract on cell growth and viability of the K562 human leukemia cell line, and to investigate possible molecular mechanisms of action. Oleuropein of 98% purity was used for our studies. We first demonstrated that K562 cells treated with 200 and 400 μg/ml oleuropein exhibited a significant reduction in cell growth and viability after four days as compared to ethanol-treated controls. Cells treated with 200μg/ml oleuropein showed decreased cell proliferation and viability after two days, and exhibited approximately 90% reduction in cell density and viability after four days of treatment. A concentration of 400 μg/ml oleuropein resulted in 100% toxicity by day four. We also examined the effects of oleuropein on cellular cytotoxicity using an LDH release assay and found a two-fold elevation in LDH release within 24 hours of treatment with 200 μg/mL oleuropein. To begin to explore a mechanisms of action, we used western blotting to examine known antioxidant and signaling pathways for possible regulation by oleuropein in these cells. We examined expression of the Peroxiredoxin (Prdx) family of proteins, a group of thiol-specific antioxidants found to be elevated in many types of cancer. We found that 200 ug/ml oleuropein reduced Prdx1 expression by about 50% after eight and twenty-four hours, while having no significant effect on expression levels of Prdx-2, -3, -4, and -6. We are currently investigating the mechanism of cell death induced by oleuropein, as well as the role of Prdx1 in oleuropein-induced toxicity. Together with previously reported cancer-cell specific effects, this research provides a promising new avenue for the use of natural products as anti-cancer agents. Citation Format: Natalie Fulco, Sophia Fagan, Shelley A. Phelan. Oleuropein reduces Prdx1 expression, cell proliferation and viability in K562 human leukemia cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1872.
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Hydroxytyrosol
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Abstract This research paper reports on the concentrations of oleuropein in fruits of seven Italian olive cultivars. These oleuropein levels, during fruit growth and maturation, were monitored by taking olive samples from the same olive trees grown in Middle Italy. A novel high‐resolution gas chromatography (HRGC) oleuropein quantification method and a new high‐performance liquid chromatography (HPLC) method were developed. The olive fruits showed high contents of oleuropein, which were greatly influenced by the olive cultivar (genetic store) factor. The stage of fruit growth and maturation was another factor strongly affecting the contents of iridoid oleuropein in olive drupes, whatever the olive cultivar considered. Green olives had much higher concentrations of this biofunctional glucoside, which decreased regularly during fruit growth and ripeness. No differences were observed between the two developed oleuropein quantification methods, which gave, for all the olive cultivars, average values of fruit oleuropein contents that were not statistically different. These two reliable repetitive methods, noticeably the HPLC one (which also showed a lower running time), could be used for routine determination of oleuropein in olive drupes. We observed that, in general, olive cultivars having high oleuropein concentrations in the fruits were also characterized by marked oleuropein contents in the leaves.
Oleuropein
Olea
Olive leaf
Oleaceae
Olive trees
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Oleuropein is one of the two main phenolic compounds derived from olive leaves. Numerous studies have found that the polyphenols contained in olive leaves possess strong antioxidant properties, and increase apoptosis in many types of cancer cells, suggesting its possible efficacy as an anti‐cancer treatments. The purpose of our study was to examine the effects of oleuropein extract on cell growth and viability of the K562 human leukemia cell line, and to investigate possible molecular mechanisms of action. Oleuropein of 98% purity was used for our studies. We first demonstrated that K562 cells treated with 200 and 400 μg/ml oleuropein exhibited a significant reduction in cell growth and viability after four days as compared to ethanol‐treated controls. Cells treated with 200μg/ml oleuropein showed decreased cell proliferation and viability after two days, and exhibited approximately 90% reduction in cell density and viability after four days of treatment. A concentration of 400 μg/ml oleuropein resulted in 100% toxicity by day four. We also examined the effects of oleuropein on cellular cytotoxicity using an LDH release assay and found a two‐fold elevation in LDH release within 24 hours of treatment with 200 μg/mL oleuropein. To begin to explore a mechanisms of action, we used western blotting to examine known antioxidant and signaling pathways for possible regulation by oleuropein in these cells. We examined expression of the Peroxiredoxin (Prdx) family of proteins, a group of thiol‐specific antioxidants found to be elevated in many types of cancer. We found that 200 ug/ml oleuropein reduced Prdx1 expression by about 50% after eight and twenty‐four hours, while having no significant effect on expression levels of Prdx‐2, ‐3, ‐4, and ‐6. We are currently investigating the mechanism of cell death induced by oleuropein, as well as the role of Prdx1 in oleuropein‐induced toxicity. Together with previously reported cancer‐cell specific effects, this research provides a promising new avenue for the use of natural products as anti‐cancer agents. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
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Hydroxytyrosol
K562 cells
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In this study, it was aimed to extract, purify oleuropein from leaves of different olive varieties and determine antioxidant and antimicrobial activity. For this purpose, olive leaf crude extract (CE), partially purified oleuropein, and purified oleuropein were obtained from leaves of Domat, Edremit, and Trilye varieties. Oleuropein amount of olive leaf products ranged between 215.26 and 958.22 mg/g. Total phenolic content in terms of gallic acid and oleuropein ranged between 102.36 and 325.02 mg gallic acid equivalent (GAE)/g and 308.06 and 915.33 mg oleuropein equivalent (OE)/g, respectively. Antioxidant activities of olive leaf products ranged between 104.83 and 456.50 mg TE/g (ABTS) and 109.27 and 456.93 mg TE/g (DPPH), respectively. MIC values ranged between 50 and 0.781 mg/ml for tested microorganism cultures. Among the microorganisms, Staphylococcus aureus is the most sensitive to oleuropein extracts, while Escherichia coli O1577:H7 is the most resistant. In conclusion, CEs and oleuropein purified from these CEs have potential to extend shelf life of food products due to their determined antioxidant and antimicrobial activities. Novelty impact statement This study focused on the extraction and purification of oleuropein compound from leaves of different olive varieties due to limited studies on purification of oleuropein in literature. A simple, cheap, and fast method was devoloped, and high purity oleuropein was obtained by applying purification processes. Also, it was determined that CEs obtained from different olive cultivar leaves and oleuropein purified from these extracts have potential to improve functional properties and extend the shelf life of food products due to their antioxidant and antimicrobial activity.
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Oleuropein is a phenolic compound found in all parts of the olive tree (Olea europaea L.), although at higher levels in the leaves. The health benefits associated with the consumption of oleuropein include the prevention of cardiac diseases, improvement in lipid metabolism, and decrease in obesity-related disturbs, among others. In addition, several studies have shown that oleuropein presents antimicrobial, antioxidant, and inflammatory properties. The scientific interest in the methods for the extraction of oleuropein from olive leaves has markedly increased in recent years, aiming to extend its application in foods, cosmetics, and drugs. In this review, the extraction procedures available in the literature are described according to their advantages and disadvantages that directly affect the extraction yield. The applicability of oleuropein in food products is also discussed.
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Seasonal variation of oleuropein content in olive leaves was investigated,and the influences of preparation and extraction factors to the yield were discussed. HPLC was used to determine the content of oleuropein. Results showed:content of oleuropein in a year has two peak periods,namely Feb. and May (among them:Feb.May),and two trough periods,namely Nov. and April. Huge differences existed among different breads. Keladi olive leaves have the highest oleuropein content of 17.2 %,in contrary,Peidaling olive leaves have the lowest oleuropein content of 1.65 %. The content of oleuropein of 20 years-old trees is much higher than that of 3 years old. Ultrasonic extraction is better than heat extraction. Natural drying of leaves superior to heat drying to obtain higher yield of oleuropein.
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Oleuropein is one of the main phenolic compounds of the olive plant, Olea europaea. It can be found in high quantities in leaves and roots (up to 500 mg/g dry extract) [1]. It is a glucosylated ester of hydroxytyrosol (HT) with the secoiridoid elenolic acid (EA). Oleuropein's various pharmacological properties have been unveiled, including antioxidant, antimicrobial, cardioprotective, hypolipidemic etc. HT is one of the most important degradation products of oleuropein, during the fruit maturation process. It is a strong antioxidant and the only olive molecule with an approved health claim from EFSA [2]. Other hydrolysis products of oleuropein are a wide range of oleuropein aglycones and EA, both possessing important biological activities, such as antioxidant, anti-inflammatory, antimicrobial, antiviral.
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Olives (Olea europaea L.) and olive oils have a significant place in the daily diet in the Mediterranean Region and contain significant amounts of polyphenolic compounds, of which. oleuropein, hydroxytyrosol and tyrosol are dominant. Harvest time, geographical region and climate all affect the phenolic content. Experimental, clinical and epidemiological studies show the beneficial effects of oleuropein, such as antioxidant, antimicrobial, anticancer anti-inflammatory, antineuropathic and other properties. In particular, olive, leaves, roots, virgin olive oil and olive mill waste (vegetation and wastewater) are potential sources of oleuropein.This review focuses on the pharmacological effects of oleuropein and extraction procedures for oleuropein
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The phenolic compound oleuropein, isolated from the olive tree (Olea europaea L.), was investigated as a crosslinking agent for collagen. Oleuropein undergoes deglucosidation by the enzyme β-glucosidase to produce an aglycone structure of
oleuropein which is the active form. Various parameters such as oleuropein concentration, enzyme concentration and incubation period were investigated. A concentration of 0.2% w/v of the oleuropein and 0.5 U/ml of the enzyme was found to be efficient and rapid under these conditions producing a denaturation temperature of 68.3oC for the collagen-oleuropein aglycone matrix
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Oleuropein
Olea
Oleaceae
Hydroxytyrosol
Olive leaf
Esterase
Glucoside
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