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Bone Protective Effect of Extra-Virgin Olive Oil Phenolic Compounds by Modulating Osteoblast Gene Expression.

ABSTRACT: The phenolic compounds of extra-virgin olive oil can act at various levels to protect individuals against cardiovascular and neurodegenerative diseases, cancer, and osteoporosis, among others. Polyphenols in extra-virgin olive oil can stimulate the proliferation of osteoblasts, modify their antigen profile, and promote alkaline phosphatase synthesis. The objective of this work was to determine the effect of different extra-virgin olive oil phenolic compounds on the gene expression of osteoblast-related markers. The cells of the MG63 osteoblast line were cultured for 24 h with 10^-6 M of the phenolic compounds ferulic acid, caffeic acid, coumaric acid, apigenin, or luteolin. The expression of studied markers was quantified using quantitative real-time polymerase chain reaction (q-RT-PCR). The expression by MG63 osteoblasts of growth and differentiation/maturation markers was modified after 24 h of treatment with 10^-6 M of the phenolic compounds under study, most of which increased the gene expression of the transforming growth factor ?1 (TGF-?1), TGF-? receptor 1,2 and 3 (TGF-?R1, TGF-?R2, TGF-?R3), bone morphogenetic protein 2 and 7 (BMP2, BMP7), run-related transcription factor 2 (RUNX-2), Alkaline phosphatase (ALP), Osteocalcin (OSC), Osterix (OSX), Collagen type I (Col-I) and osteoprotegerin (OPN). The extra-virgin olive oil phenolic compounds may have a beneficial effect on bone by modulating osteoblast physiology, which would support their protective effect against bone pathologies.

SUBMITTER: Melguizo-Rodriguez L

PROVIDER: S-EPMC6722737 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Bone Protective Effect of Extra-Virgin Olive Oil Phenolic Compounds by Modulating Osteoblast Gene Expression.

Melguizo-Rodríguez Lucía L Manzano-Moreno Francisco Javier FJ Illescas-Montes Rebeca R Ramos-Torrecillas Javier J Luna-Bertos Elvira de E Ruiz Concepción C García-Martínez Olga O

Nutrients 20190725 8

The phenolic compounds of extra-virgin olive oil can act at various levels to protect individuals against cardiovascular and neurodegenerative diseases, cancer, and osteoporosis, among others. Polyphenols in extra-virgin olive oil can stimulate the proliferation of osteoblasts, modify their antigen profile, and promote alkaline phosphatase synthesis. The objective of this work was to determine the effect of different extra-virgin olive oil phenolic compounds on the gene expression of osteoblast- ...[more]

PMID: 31349732

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Project description:BackgroundThe effects of the olive oil-rich Mediterranean diet on breast cancer risk might be underestimated when HER2 (ERBB2) oncogene-positive and HER2-negative breast carcinomas are considered together. We here investigated the anti-HER2 effects of phenolic fractions directly extracted from Extra Virgin Olive Oil (EVOO) in cultured human breast cancer cell lines.MethodsSolid phase extraction followed by semi-preparative high-performance liquid chromatography (HPLC) was used to isolate phenolic fractions from commercial EVOO. Analytical capillary electrophoresis coupled to mass spectrometry was performed to check for the composition and to confirm the identity of the isolated fractions. EVOO polyphenolic fractions were tested on their tumoricidal ability against HER2-negative and HER2-positive breast cancer in vitro models using MTT, crystal violet staining, and Cell Death ELISA assays. The effects of EVOO polyphenolic fractions on the expression and activation status of HER2 oncoprotein were evaluated using HER2-specific ELISAs and immunoblotting procedures, respectively.ResultsAmong the fractions mainly containing the single phenols hydroxytyrosol and tyrosol, the polyphenol acid elenolic acid, the lignans (+)-pinoresinol and 1-(+)-acetoxypinoresinol, and the secoiridoids deacetoxy oleuropein aglycone, ligstroside aglycone, and oleuropein aglycone, all the major EVOO polyphenols (i.e. secoiridoids and lignans) were found to induce strong tumoricidal effects within a micromolar range by selectively triggering high levels of apoptotic cell death in HER2-overexpressors. Small interfering RNA-induced depletion of HER2 protein and lapatinib-induced blockade of HER2 tyrosine kinase activity both significantly prevented EVOO polyphenols-induced cytotoxicity. EVOO polyphenols drastically depleted HER2 protein and reduced HER2 tyrosine autophosphorylation in a dose- and time-dependent manner. EVOO polyphenols-induced HER2 downregulation occurred regardless the molecular mechanism contributing to HER2 overexpression (i.e. naturally by gene amplification and ectopically driven by a viral promoter). Pre-treatment with the proteasome inhibitor MG132 prevented EVOO polyphenols-induced HER2 depletion.ConclusionThe ability of EVOO-derived polyphenols to inhibit HER2 activity by promoting the proteasomal degradation of the HER2 protein itself, together with the fact that humans have safely been ingesting secoiridoids and lignans as long as they have been consuming olives and OO, support the notion that the stereochemistry of these phytochemicals might provide an excellent and safe platform for the design of new HER2-targeting agents.

Dataset Information

Bone Protective Effect of Extra-Virgin Olive Oil Phenolic Compounds by Modulating Osteoblast Gene Expression.

Publications

Bone Protective Effect of Extra-Virgin Olive Oil Phenolic Compounds by Modulating Osteoblast Gene Expression.

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