New semi-synthetic analogs of oleuropein show improved anticancer activity in vitro and in vivo

Samara, Pinelopi; Christoforidou, Nikoleta; Lémus, Christelle; Argyropoulou, Aikaterini; Ioannou, Kyriaki; Vougogiannopoulou, Konstantina; Aligiannis, Nektarios; Paronis, Efthymios; Gaboriaud‐Kolar, Nicolas; Tsitsilonis, Ourania E.; Skaltsounis, Alexios‐Léandros

doi:10.1016/j.ejmech.2017.05.029

Cited by 28 publications

(33 citation statements)

References 34 publications

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“…Thus, the inhibition of glycolysis by OLEO acquires a great significance for the targeting of cancer cell growth and expansion. Our findings, together with previous evidence showing the anti-cancer effects exerted by OLEO, pure Ole and analogs [23,53,54], reinforce the hypothesis to propose the use of these natural compounds in combination with conventional therapy used in the treatment of cancer.…”

Section: Discussionsupporting

confidence: 86%

Cancer Glycolytic Dependence as a New Target of Olive Leaf Extract

Ruzzolini

Peppicelli

Bianchini

et al. 2020

Cancers

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Oleuropein (Ole), the main bioactive phenolic component of Olea europaea L. has recently attracted the scientific attention for its several beneficial properties, including its anticancer effects. This study is intended to investigate whether an olive leaf extract enriched in Ole (OLEO) may counteract the aerobic glycolysis exploited by tumor cells. We found that OLEO decreased melanoma cell proliferation and motility. OLEO was also able to reduce the rate of glycolysis of human melanoma cells without affecting oxidative phosphorylation. This reduction was associated with a significant decrease of glucose transporter-1, protein kinase isoform M2 and monocarboxylate transporter-4 expression, possible drivers of such glycolysis inhibition. Extending the study to other tumor histotypes, we observed that the metabolic effects of OLEO are not confined to melanoma, but also confirmed in colon carcinoma, breast cancer and chronic myeloid leukemia. In conclusion, OLEO represents a natural product effective in reducing the glycolytic metabolism of different tumor types, revealing an extended metabolic inhibitory activity that may be well suited in a complementary anti-cancer therapy.

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Section: Discussionsupporting

confidence: 86%

Cancer Glycolytic Dependence as a New Target of Olive Leaf Extract

Ruzzolini

Peppicelli

Bianchini

et al. 2020

Cancers

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“…Samara et al [142] studied 51 analogs of Ole on several human cancer cells, and found that analog 24, non-toxic for normal cells, expresses the highest level of inhibitory activity in vitro (human colon cancer cells HCT-116, human cervical carcinoma cells HeLa, MCF-7 cells) as well as in vivo (B16-F10 mouse melanoma cells). Of a particular importance was the finding that Ole analog 24 expresses a promotion of natural immune responses, from Natural Killer cells and Limphokine-activated Killer cells.…”

Section: Pro-apoptotic and Anti-proliferative Effects Of Oleuropeinmentioning

confidence: 99%

Oleuropein, a Bioactive Compound from Olea europaea L., as a Potential Preventive and Therapeutic Agent in Non-Communicable Diseases

et al. 2019

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Growing scientific literature data suggest that the intake of natural bioactive compounds plays a critical role in preventing or reducing the occurrence of human chronic non-communicable diseases (NCDs). Oleuropein, the main phenolic component of Olea europaea L., has attracted scientific attention for its several health beneficial properties such as antioxidant, anti-inflammatory, cardio- and neuro-protective, and anti-cancer. This article is a narrative review focused on the current literature concerning the effect of oleuropein in NCDs, such as neuro- and cardiovascular diseases, diabetes mellitus, chronic kidney diseases, and cancer, by its putative antioxidant and anti-inflammatory activity, but also for its other peculiar actions such as an autophagy inducer and amyloid fibril growth inhibitor and, finally, for its anti-cancer effect. Despite the increasing number of published studies, looking at the beneficial effects of oleuropein, there is limited clinical evidence focused on the benefits of this polyphenol as a nutraceutical product in humans, and many problems are still to be resolved about its bioavailability, bioaccessibility, and dosage. Thus, future clinical randomized trials are needed to establish the relation between the beneficial effects and the mechanisms of action occurring in the human body in response to the intake of oleuropein.

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“…It is likely that Ole might boost up the inhibition of mTOR also through the AMPK/mTOR pathway, that in this study was not investigated, but that was suggested by our previous finding and by other authors [42,52]. In addition, Ole may inhibit, tumor angiogenesis and in vivo tumor growth, respectively as recently found by Song's et al [48] and Samara's et al [53] studies.…”

Section: Discussionmentioning

confidence: 48%

“…Netherless, polyphenols bioavailability is still a big drawback that many studies try to overcome through different approaches including the construction of granules containing probiotics and Olea Europaea extract in order to increase polyphenols bioavailability [62], and the synthesis of Ole analogs with various chemical properties and more active than Ole [53].…”

Section: Discussionmentioning

confidence: 99%

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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New semi-synthetic analogs of oleuropein show improved anticancer activity in vitro and in vivo

Cited by 28 publications

References 34 publications

Cancer Glycolytic Dependence as a New Target of Olive Leaf Extract

Cancer Glycolytic Dependence as a New Target of Olive Leaf Extract

Oleuropein, a Bioactive Compound from Olea europaea L., as a Potential Preventive and Therapeutic Agent in Non-Communicable Diseases

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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