Protective role of oleuropein and its metabolite hydroxytyrosol on cancer

Carrera-González, María Pilar; Ramírez-Expósito, María Jesús; Mayas, Marı́a Dolores; Martínez-Martos, José Manuel

doi:10.1016/j.tifs.2013.03.003

Cited by 66 publications

(46 citation statements)

References 62 publications

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“…However, the earlier-eluting less polar peaks (1-7) were slightly larger in the water extract while the later-eluting more polar peaks (9)(10)(11)(12)(13)(14)(15)(16)(17) were larger in the ethanol and methanol extracts. The greatest effect was seen in peak 12, for which the area was more than tripled in the ethanol and methanol extracts compared to the water extract.…”

Section: The Influence Of Extraction Methods On Phytochemical Propertiesmentioning

confidence: 90%

“…More recently, oleuropein has been investigated for its potent anti-cancer activity. It has been shown to inhibit proliferation and migration of a number of advanced grade human tumour cell lines in a dose dependent manner [6][7][8][9][10][11]. However, the effect of olive phenolic compounds has yet to be investigated for pancreatic cancer.…”

Section: Introductionmentioning

confidence: 99%

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Phytochemical Properties and Anti-Proliferative Activity of Olea europaea L. Leaf Extracts against Pancreatic Cancer Cells

Goldsmith¹,

Vuong²,

Sadeqzadeh

et al. 2015

Molecules

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Olea europaea L. leaves are an agricultural waste product with a high concentration of phenolic compounds; especially oleuropein. Oleuropein has been shown to exhibit anti-proliferative activity against a number of cancer types. However, they have not been tested against pancreatic cancer, the fifth leading cause of cancer related death in Western countries. Therefore, water, 50% ethanol and 50% methanol extracts of Corregiola and Frantoio variety Olea europaea L. leaves were investigated for their total phenolic compounds, total flavonoids and oleuropein content, antioxidant capacity and anti-proliferative activity against MiaPaCa-2 pancreatic cancer cells. The extracts only had slight differences in their phytochemical properties, and at 100 and 200 μg/mL, all decreased the viability of the pancreatic cancer cells relative to controls. At 50 μg/mL, the water extract from the Corregiola leaves exhibited the highest anti-proliferative activity with the effect possibly due to early eluting HPLC peaks. For this reason, olive leaf extracts warrant further investigation into their potential anti-pancreatic cancer benefits.

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Section: The Influence Of Extraction Methods On Phytochemical Propertiesmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Phytochemical Properties and Anti-Proliferative Activity of Olea europaea L. Leaf Extracts against Pancreatic Cancer Cells

Goldsmith¹,

Vuong²,

Sadeqzadeh

et al. 2015

Molecules

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“…Recent studies indicate that the AKT signaling pathway is overactive in many cancers, and inhibition of this pathway is considered as a novel target for cancer therapy (46). One study demonstrated that oleuropein is implicated as a negative regulator of proliferation of glioma cells (47). However, the underlying mechanisms through which oleuropein exerts its antitumor effects are not clear.…”

Section: Discussionmentioning

confidence: 99%

Oleuropein inhibits the proliferation and invasion of glioma cells via suppression of the AKT signaling pathway

et al. 2016

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Oleuropein, the main phenolic compound of secoiridoids, has been proven to have inhibitory effects on various types of cancers. However, the antitumor effects and related mechanisms in glioma remain unclear. In the present study, U251 and A172 cells were used to assess the effects of oleuropein. Using cell viability assay, we found that oleuropein greatly inhibited the viability of the U251 and A172 cells. Additionally, flow cytometric apoptosis assay indicated that oleuropein induced the apoptosis of the two cell lines. Consistently, the inhibitory effects of oleuropein on migration and invasion were also observed in vitro. In regards to the mechanism, we found that oleuropein significantly decreased phosphorylation of AKT (p-AKT), accompanied by upregulation of Bax and downregulation of Bcl-2. We also found that there was a decrease in the expression levels of matrix metalloproteinase-2 (MMP-2) and MMP-9 after treatment with oleuropein. Furthermore, a specific phosphatidylinositol 3 kinase (PI3K) inhibitor, LY294002, enhanced the pro-apoptotic and anti-invasive effects induced by oleuropein, which suggested that oleuropein suppressed the growth and invasion of glioma cells via inhibition of AKT activity. Taken together, our results indicated that treatment with oleuropein may be an effective therapy for malignant glioma through suppression of tumor proliferation and invasion by inhibition of the AKT signaling pathway.

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“…Furthermore our results suggest that an easily available product as an olive leaf extract enriched in Ole could be even more effective than Ole alone, probably because of the co-presence of other polyphenols among which hydroxityrosol that many authors suggested to be the real active Ole metabolic product [23,29,30]. So olive leaf extracts seems to have a powerful anticancer property as also Samet I. et al and Mijatovic SA et al shown about human chronic myelogenous leukemia K562 and melanoma cells respectively [60,61], and their mixed phenolic composition with an enrichment in Ole could be useful to decrease the in vitro doses to obtain the same effect of Ole administration alone at higher concentration.…”

Section: Discussionmentioning

confidence: 73%

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

Ruzzolini¹,

Peppicelli²,

Andreucci³

et al. 2018

Preprint

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Oleuropein (Ole), a secoiridoid glucoside present in Olea europaea leaves, gained the interest of many scientists thanks to its several biological properties, including the anticancer one. We verified whether Ole might potentiate cytotoxicity of conventional drugs used to treat melanoma, disclosing new potential 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 in melanoma cells, while at a non-toxic dose of 250 μM, it affected cell proliferation and induced the downregulation of pAKT/pS6 pathway. 250 μM Ole did not potentiate the effect of Vemurafenib (PLX4032), but it succeeded in increase the cytotoxic effect of Dacarbazine (DTIC). The mayor effect was found in the association between Ole and Everolimus (RAD001), also on PLX4032-resistant BRAF melanoma cells, possibly cooperating in the inhibition of pAKT/pS6 pathway. Of interest, an olive leaf extract enriched in equimolar Ole was more effective and able to further improve DTIC and, particularly, RAD001 efficacy on BRAF melanoma cells than Ole alone. Therefore, Ole represents a natural product able to potentiate a wide array of chemotherapeutics against BRAF melanoma cells affecting pAKT/pS6 pathway.

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Protective role of oleuropein and its metabolite hydroxytyrosol on cancer

Cited by 66 publications

References 62 publications

Phytochemical Properties and Anti-Proliferative Activity of Olea europaea L. Leaf Extracts against Pancreatic Cancer Cells

Phytochemical Properties and Anti-Proliferative Activity of Olea europaea L. Leaf Extracts against Pancreatic Cancer Cells

Oleuropein inhibits the proliferation and invasion of glioma cells via suppression of the AKT signaling pathway

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

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