Olea europaea leaf extract and bevacizumab synergistically exhibit beneficial efficacy upon human glioblastoma cancer stem cells through reducing angiogenesis and invasion in vitro

Tezcan, Gülçin; Taşkapılıoğlu, Mevlüt Özgür; Tunca, Berrin; Bekâr, Ahmet; Demirci, Hilal; Kocaelı, Hasan; Aksoy, Seçil Ak; Egelí, Ünal; Çeçener, Gülşah; Tolunay, Şahsine

doi:10.1016/j.biopha.2017.04.022

Cited by 12 publications

(9 citation statements)

References 74 publications

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“…However, this treatment often promotes an enhanced aggressive phenotype in resistant GBM cells. Tezcan et al [160] were able to demonstrate that Ole synergistically increases bevacizumab's anti-angiogenesis and anti-migration effects. Ole has the ability to promote the effects of bevacizumab, preventing VEGFA, MMP-2 and -9 activities.…”

Section: Chemiotherapy Potentiation By 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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Section: Chemiotherapy Potentiation By 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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“…Epigallocatechin gallate from green tea synergizes with temozolomide to inhibit viability, migration, and drug resistance of glioma stem-like cells isolated from the U87 line . The anti-invasive activity of a medicinal herbal extract from olive (Olea) leaf on glioblastoma stem cells derived from human primary tumors was increased when given in combination with bevacuazimab (Tezcan et al, 2017a). Further work seems likely to demonstrate that the most effective clinical strategies will include co-administration of multiple agents, targeted to subtype-specific panels of factors in glioblastoma, to enhance the successful outcomes of interventions.…”

Section: Pharmacological Targets For Cancer Treatmentmentioning

confidence: 99%

“…These observations point to an important gap in knowledge regarding the ion channel and receptor modulatory effects of anti-cancer medicinal herb extracts. It is interesting to note that some compounds such as curcumin [1.25 µg/ml] (Yin et al, 2014), OLE extract [1 mg/ml] (Tezcan et al, 2017a), resveratrol [10 µM] and quercetin [30 µmol/L] when tested in combination with temozolomide have been effective in increasing survival in animal models, overcoming temozolomide resistance by increasing ROS production, disrupting AKT/mTOR signaling, reducing MGMT gene expression, suppressing Hsp27 protein expression, and downregulating the expression of MMP-2 and -9. The plant derived compounds are effective in low doses and intriguingly the effective concentration of temozolomide required in combination is also reduced (50-100 µM) leading to more effective treatments with fewer side effects.…”

Section: Natural Plant Products As Sources Of Therapeutic Agentsmentioning

confidence: 99%

Molecular Targets for Combined Therapeutic Strategies to Limit Glioblastoma Cell Migration and Invasion

Yool

Ramesh

2020

Front. Pharmacol.

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The highly invasive nature of glioblastoma imposes poor prospects for patient survival. Molecular evidence indicates glioblastoma cells undergo an intriguing expansion of phenotypic properties to include neuron-like signaling using excitable membrane ion channels and synaptic proteins, augmenting survival and motility. Neurotransmitter receptors, membrane signaling, excitatory receptors, and Ca 2+ responses are important candidates for the design of customized treatments for cancers within the heterogeneous central nervous system. Relatively few published studies of glioblastoma multiforme (GBM) have evaluated pharmacological agents targeted to signaling pathways in limiting cancer cell motility. Transcriptomic analyses here identified classes of ion channels, ionotropic receptors, and synaptic proteins that are enriched in human glioblastoma biopsy samples. The pattern of GBM-enriched gene expression points to a major role for glutamate signaling. However, the predominant role of AMPA receptors in fast excitatory signaling throughout the central nervous system raises a challenge on how to target inhibitors selectively to cancer cells while maintaining tolerability. This review critically evaluates a panel of ligand-and voltage-gated ion channels and synaptic proteins upregulated in GBM, and the evidence for their potential roles in the pathological disease progress. Evidence suggests combinations of therapies could be more effective than single agents alone. Natural plant products used in traditional medicines for the treatment of glioblastoma contain flavonoids, terpenoids, polyphenols, epigallocatechin gallate, quinones, and saponins, which might serendipitously include agents that modulate some classes of signaling compounds highlighted in this review. New therapeutic strategies are likely to exploit evidence-based combinations of selected agents, each at a low dose, to create new cancer cell-specific therapeutics. A BFIGURE 1 | Illustration of a sample distribution of published glioblastoma studies suggesting less than 3% combine three themes (inhibitor, proliferation, motility). Venn diagram (A) summarizing the numbers of published articles on glioblastoma, with key words linked to inhibition,

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“…In our previous studies and other studies, the effect of plant extracts on gene regulation through modified miRNA regulation was demonstrated. [8][9][10][11] Therefore, we evaluated differences in miRNA expression due to OL and compared them with those due to OLE in GBM cells. A brief comparative summary of the difference between the effects of OLE and OL is presented in Table 3.…”

Section: Discussionmentioning

confidence: 99%

Oleuropein modulates glioblastoma miRNA pattern different from Olea europaea leaf extract

et al. 2019

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Glioblastoma (GBM) is the most prevalent and deadliest subtype of glioma. Despite current innovations in existing therapeutic modalities, GBM remains incurable, and alternative therapies are required. Previously, we demonstrated that Olea europaea leaf extract (OLE) kills GBM cells by modulating miR-181b, miR-137, miR-153 and Let-7d expression. However, although oleuropein (OL) is the main compound in OLE, its role in the antitumour effect of OLE remains unknown. This study determined the effect of OL on GBM cell line T98G and compared the results with our previous findings regarding the effect of OLE on the same cell line. The antiproliferative activity of OL and its effect on temozolomide (TMZ) response were tested inT98G cells using WST-1 assay. OL inhibition was evaluated using one-way analysis of variance with Tukey’s post hoc test. The effect of OL on miR-181b, miR-137, miR-153 and Let-7d expression was assessed using quantitative reverse transcription polymerase chain reaction. Fold differences in expression between untreated, OL or OL + TMZ-treated samples were calculated using 2−ΔCt method. Significance was evaluated using an independent sample t-test. Treatment with 277.5 and 555 µM OL resulted in 39.51% and 75.40% reductions in T98G cells within 24 h. Coadministration of 325 µM TMZ and 277.5 or 555 µM, OL caused 2.08- and 2.83-fold increases, respectively, in the therapeutic effect of TMZ. OL + TMZ significantly increased microRNA expression, particularly Let-7d, than OLE. In conclusion, OL has an antitumour effect on GBM cells mainly via regulation of Let-7d expression. The present results also indicate other minor compounds in OLE play important anticancer roles.

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Olea europaea leaf extract and bevacizumab synergistically exhibit beneficial efficacy upon human glioblastoma cancer stem cells through reducing angiogenesis and invasion in vitro

Cited by 12 publications

References 74 publications

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

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

Molecular Targets for Combined Therapeutic Strategies to Limit Glioblastoma Cell Migration and Invasion

Oleuropein modulates glioblastoma miRNA pattern different from Olea europaea leaf extract

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