Hydroxytyrosol inhibits cancer stem cells and the metastatic capacity of triple-negative breast cancer cell lines by the simultaneous targeting of epithelial-to-mesenchymal transition, Wnt/β-catenin and TGFβ signaling pathways

Cruz-Lozano, Marina; González-González, Adrián; Marchal, Juan Antonio; Muñoz-Muela, Esperanza; Molina, Maria P.; Cara, Francisca E.; Brown, Anthony M.; García‐Rivas, Gerardo; Hernández-Brenes, Carmen; Lorente, José A.; Sánchez‐Rovira, Pedro; Chang, Jenny C.; Granados-Principal, Sergio

doi:10.1007/s00394-018-1864-1

Cited by 48 publications

(34 citation statements)

References 62 publications

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“…Previous studies had highlighted an anti-tumorigenic potential of hydroxytyrosol due to its capacity to protect against oxidative DNA damage in non-malignant MCF10A breast cells ( 113 ). More recently, hydroxytyrosol was shown to have inhibitory effects on breast cancer stem cell (BCSC) self-renewal in a comprehensive investigation using multiple TNBC cell lines ( 57 ). Tumor enrichment of BCSC has been suggested to play a role in the aggressiveness and poor prognosis associated with TNBC ( 114 ).…”

Section: Olive Oil and Tnbc: Reviewmentioning

confidence: 99%

“…Tumor enrichment of BCSC has been suggested to play a role in the aggressiveness and poor prognosis associated with TNBC ( 114 ). Hydroxytyrosol at a range of concentrations (0.5–100 μM) suppressed mammosphere-forming efficiency, a marker of BCSC self-renewal, of the TNBC cell lines SUM159PT, BT549, MDA-MB-231, and Hs578T ( 57 ). In fact, the 0.5 μM dose was sufficient to suppress mammosphere formation of SUM159PT cells by 40% and the three other TNBC cell lines (BT549, MDA-MB-231, and Hs578T) by 50% after 72 h in culture.…”

Section: Olive Oil and Tnbc: Reviewmentioning

confidence: 99%

“…In BT549 and MDA-MB-231 cells, these effects were observed in parallel with dose-dependent reductions in phosphorylated LRP6, LRP6, and β-catenin by hydroxytyrosol treatment, which suggested suppression of Wnt/β-catenin signaling. Moreover, hydroxytyrosol treatment was shown to inhibit TGFβ/SMAD2/3-mediated EMT ( 57 ).…”

Section: Olive Oil and Tnbc: Reviewmentioning

confidence: 99%

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Do Olive and Fish Oils of the Mediterranean Diet Have a Role in Triple Negative Breast Cancer Prevention and Therapy? An Exploration of Evidence in Cells and Animal Models

et al. 2020

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Breast cancer is the most common malignancy and cause of cancer-related mortality among women worldwide. Triple negative breast cancers (TNBC) are the most aggressive and lethal of the breast cancer molecular subtypes, due in part to a poor understanding of TNBC etiology and lack of targeted therapeutics. Despite advances in the clinical management of TNBC, optimal treatment regimens remain elusive. Thus, identifying interventional approaches that suppress the initiation and progression of TNBC, while minimizing side effects, would be of great interest. Studies have documented an inverse relationship between the incidence of hormone receptor negative breast cancer and adherence to a Mediterranean Diet, particularly higher consumption of fish and olive oil. Here, we performed a review of studies over the last 5 years investigating the effects of fish oil, olive oil and their components in model systems of TNBC. We included studies that focused on the fish oil ω-3 essential fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) in addition to olive oil polyphenolic compounds and oleic acid. Both beneficial and deleterious effects on TNBC model systems are reviewed and we highlight how multiple components of these Mediterranean Diet oils target signaling pathways known to be aberrant in TNBC including PI3K/Akt/mTOR, NF-κB/COX2 and Wnt/β-catenin.

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Section: Olive Oil and Tnbc: Reviewmentioning

confidence: 99%

Section: Olive Oil and Tnbc: Reviewmentioning

confidence: 99%

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Do Olive and Fish Oils of the Mediterranean Diet Have a Role in Triple Negative Breast Cancer Prevention and Therapy? An Exploration of Evidence in Cells and Animal Models

et al. 2020

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“…Extra virgin olive oil (EVOO), the major source of fatty acids in the traditional Mediterranean diet, is rich in phenolic compounds, such as secoiridoid derivatives of 2‐(3,4‐dihydroxyphenyl)ethanol (hydroxytyrosol, HTy) and hydroxytyrosyl acetate (HTy‐Ac), which have a wide range of anti‐inflammatory, anti‐oxidant, and chemopreventive function in vitro . These beneficial properties were confirmed in vivo in animal models of autoimmunity …”

Section: Introductionmentioning

confidence: 97%

Olive‐Oil‐Derived Polyphenols Effectively Attenuate Inflammatory Responses of Human Keratinocytes by Interfering with the NF‐κB Pathway

Aparicio‐Soto

Redhu

Sánchéz-Hidalgo

et al. 2019

Molecular Nutrition Food Res

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Scope: Extra virgin olive oil (EVOO) is rich in phenolic compounds, including hydroxytyrosol (HTy) and hydroxytyrosyl acetate (HTy-Ac), which have presented multiple beneficial properties. Their impact on inflammatory responses in human keratinocytes and modes of action have not been addressed yet. Methods and results: Primary human keratinocytes are pretreated with HTy-Ac or HTy for 30 min and stimulated with IL-1 or Toll-like receptor 3 ligand (TLR3-l). Thymic stromal lymphopoietin (TSLP), measured by ELISA, is attenuated by both polyphenols in a dose-dependent manner. The expression of several inflammation-related genes, including distinct TSLP isoforms and IL-8, are assessed by quantitative RT-PCR and likewise inhibited by HTy-Ac/HTy. Mechanistically, EVOO phenols counteracts I B degradation and translocation of NF-B to the nucleus, a transcription factor of essential significance to TSLP and IL-8 transcriptional activity; this is evidenced by immunoblotting. Accordingly, NF-B recruitment to critical binding sites in the TSLP and IL-8 promoter is impeded in the presence of HTy-Ac/HTy, as demonstrated by chromatin immunoprecipitation. Promoter reporter assays finally reveal that the neutralizing effect on NF-B induction has functional consequences, resulting in reduced NF-B-directed transcription.

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“…The main phenolic alcohol is hydroxytyrosol (HT). Several studies have demonstrated the beneficial properties of this compound in a number of models and cancer linked events 19 , particularly in breast cancer [20][21][22] . In fact, we have recently described that hypoxia modulates the antioxidant effect of HT in MCF-7 breast cancer cells 23 .…”

mentioning

confidence: 99%

Crosstalk between hydroxytyrosol, a major olive oil phenol, and HIF-1 in MCF-7 breast cancer cells

Calahorra

Martı́nez-Lara

Granadino‐Roldán

et al. 2020

Sci Rep

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Olive oil intake has been linked with a lower incidence of breast cancer. Hypoxic microenvironment in solid tumors, such as breast cancer, is known to play a crucial role in cancer progression and in the failure of anticancer treatments. HIF-1 is the foremost effector in hypoxic response, and given that hydroxytyrosol (HT) is one of the main bioactive compounds in olive oil, in this study we deepen into its modulatory role on HIF-1. Our results in MCF-7 breast cancer cells demonstrate that HT decreases HIF-1α protein, probably by downregulating oxidative stress and by inhibiting the PI3K/ Akt/mTOR pathway. Strikingly, the expression of HIF-1 target genes does not show a parallel decrease. Particularly, adrenomedullin and vascular endothelial growth factor are up-regulated by high concentrations of HT even in HIF-1α silenced cells, pointing to HIF-1-independent mechanisms of regulation. In fact, we show, by in silico modelling and transcriptional analysis, that high doses of HT may act as an agonist of the aryl hydrocarbon receptor favoring the induction of these angiogenic genes. In conclusion, we suggest that the effect of HT in a hypoxic environment is largely affected by its concentration and involves both HIF-1 dependent and independent mechanisms.

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Hydroxytyrosol inhibits cancer stem cells and the metastatic capacity of triple-negative breast cancer cell lines by the simultaneous targeting of epithelial-to-mesenchymal transition, Wnt/β-catenin and TGFβ signaling pathways

Cited by 48 publications

References 62 publications

Do Olive and Fish Oils of the Mediterranean Diet Have a Role in Triple Negative Breast Cancer Prevention and Therapy? An Exploration of Evidence in Cells and Animal Models

Do Olive and Fish Oils of the Mediterranean Diet Have a Role in Triple Negative Breast Cancer Prevention and Therapy? An Exploration of Evidence in Cells and Animal Models

Olive‐Oil‐Derived Polyphenols Effectively Attenuate Inflammatory Responses of Human Keratinocytes by Interfering with the NF‐κB Pathway

Crosstalk between hydroxytyrosol, a major olive oil phenol, and HIF-1 in MCF-7 breast cancer cells

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