porque no todos los alimentos funcionales son procesados, aquí una muestra de los beneficios de nuestro oro líquido.

Nos complace compartir con vosotros el premio que recibieron los investigadores del CIDAF por su estudio sobre aceite de oliva y salud.

El título del proyecto es:

extra virgin olive oil polyphenols: a natural source of new epigenetic drugs against breast cancer

(Polifenoles del Aceite de Oliva Virgen Extra: Una Fuente Natural de Nuevos Fármacos Epigenéticos contra el Cáncer de Mama)

ABSTRACT

We have employed high-throughput techniques to identify the molecular biology behind the growth inhibitory effects of Extra Virgin Olive Oil (EVOO)-derived crude phenolic extracts (PE) against breast cancer (BC) cells naturally exhibiting de novo cross-resistance to moleculartargeted drugs. EVOO PE-induced BC cell growth inhibition positively correlated with a higher presence of the complex polyphenols secoiridoids instead of lignans. The use of Agilent’s whole human genome arrays followed by GSEA-based screening of the KEGG pathway database revealed a differential modulation of the BC transcriptome at the level of the cell cycle & p53 pathways. EVOO PE differentially impacted the expression status of stress-sensing, G2-M checkpoint-related GADD45 genes and of p53-related CDKN1ACDKN1C, andPMAIP-1 genes. Cell cycle and fluorescence microscopy analyses confirmed that secoiridoids-rich EVOO PE inhibited mitosis to promote G2-M cell cycle arrest. This was accompanied with the appearance of diffuse, even, DNA staining with g-H2AX and pan-nuclear hyperacetylation of Histone H3 at Lysine 18. Secoiridoids-rich EVOO PE differentially hyperactivated p38 MAPK, a GADD45-related kinase involved in Histone H3 acetylation. Oleaceae secoiridoids appear to permit histones to remain in hyperacetylated states and through the resulting alterations in gene regulation to reduce mitotic viability and metabolic competence of human breast cancer cells.

En el centro se está llevando a cabo un estudio exhaustivo referente a todo lo que concierne al aceite de oliva, desde la caracterización de diversas variedades nacionales e internacionales, así como el estudio de las mismas y su potencial efecto beneficioso sobre la salud.

Así, algunos de los estudios más recientes llevados a cabo en estos dos últimos años se muestran a continuación:

Wastes Generated during the Storage of Extra Virgin Olive Oil as a Natural Source of Phenolic Compounds. (J. Agric. Food Chem, 2011, 59 (21), pp 11491-11500)

Abstract:

Phenolic compounds in extra virgin olive oil (EVOO) have been associated with beneficial effects for health. Indeed, these compounds exert strong antiproliferative effects on many pathological processes, which has stimulated chemical characterization of the large quantities of wastes generated during olive oil production. In this investigation, the potential of byproducts generated during storage of EVOO as a natural source of antioxidant compounds has been evaluated using solid–liquid and liquid–liquid extraction processes followed by rapid resolution liquid chromatography (RRLC) coupled to electrospray time-of-flight and ion trap mass spectrometry (TOF/IT-MS). These wastes contain polyphenols belonging to different classes such as phenolic acids and alcohols, secoiridoids, lignans, and flavones. The relationship between phenolic and derived compounds has been tentatively established on the basis of proposed degradation pathways. Finally, qualitative and quantitative characterizations of solid and aqueous wastes suggest that these byproducts can be considered an important natural source of phenolic compounds, mainly hydroxytyrosol, tyrosol, decarboxymethyl oleuropein aglycone, and luteolin, which, after suitable purification, could be used as food antioxidants or as ingredients in nutraceutical products due to their interesting technological and pharmaceutical properties.

Crude phenolic extracts from extra virgin olive oil circumvent de novo breast cancer resistance to HER1/HER2-targeting drugs by inducing GADD45-sensed cellular stress, G2/M arrest and hyperacetylation of Histone H3(International Journal of Oncology, 38 (6), pp 1533-1547)

Abstract:

Characterization of the molecular function of complex phenols naturally present in extra virgin olive oil (EVOO) against the HER2-gene amplified JIMT-1 cell line, a unique breast cancer model that inherently exhibits cross-resistance to multiple HER1/2-targeted drugs including trastuzumab, gefitinib, erlotinib and lapatinib, may underscore innovative cancer molecules with novel therapeutic targets because they should efficiently circumvent de novo resistance to HER1/2 inhibitors in order to elicit tumoricidal effects. We identified pivotal signaling pathways associated with the efficacy of crude phenolic extracts (PEs) obtained from 14 monovarietals of Spanish EVOOs. i) MTT-based cell viability and HPLC coupled to time-of-flight (TOF) mass spectrometry assays revealed that anti-cancer activity of EVOO PEs positively correlated with the phenolic index (i.e., total content of phenolics) and with a higher presence of the complex polyphenols secoiridoids instead of lignans. ii) Genome-wide analyses using 44 K Agilent’s whole human arrays followed by Gene Set Enrichment Analysis (GSEA)-based screening of the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database revealed a differential modulation of the JIMT-1 transcriptome at the level of the cell cycle and p53 pathways. EVOO PEs differentially impacted the expression status of stress-sensing, G2-M check-point-related GADD45 genes and of p53-related CDKN1A, CDKN1C and PMAIP-1 genes. iii) Cell cycle and fluorescence microscopy analyses confirmed that secoiridoid-rich EVOO PE inhibited mitosis to promote G2-M cell cycle arrest. This was accompanied with the appearance of diffuse, even DNA staining with γH2AX and pan-nuclear hyperacetylation of Histone H3 at Lysine 18. iv) Semi-quantitative Signaling Node Multi-Target ELISAs determined that secoiridoid-rich EVOO PE drastically activated the mitogen-activated protein kinases MEK1 and p38 MAPK, a GADD45-related kinase involved in Histone H3 acetylation. Secoiridoids, a family of complex polyphenols characteristic of Oleaceae plants, appear to permit histones to remain in hyperacetylated states and through the resulting alterations in gene regulation to reduce mitotic viability and metabolic competence of breast cancer cells inherently refractory to HER-targeting therapies ab initio. Oleaceae secoiridoids could provide a valuable phytochemical platform for the design of more pharmacologically active second-generation phytopharmaceutical anti-breast cancer molecules with a unique mode of action.

Prediction of Extra Virgin Olive Oil Varieties through Their Phenolic Profile. Potential Cytotoxic Activity against Human Breast Cancer Cells. (J. Agric. Food Chem, 2010, 58 (18), pp 9942-9955)

Abstract:

The aim of this work was to develop a rapid resolution liquid chromatography coupled to electrospray ionization time-of-flight mass spectrometry (RRLC-ESI-TOF-MS) method followed by tetrazolium salt (MTT)-based cell viability assays for qualitative and quantitative classification of extra virgin olive oil (EVOO) varieties by phenolic and other polar compound contents as well as for rapid characterization of putative cytotoxic activities against human cancer cells. Five different Spanish EVOO varieties were analyzed, and RRLC-ESI-TOF-MS method was applied for qualitative and quantitative identification of most important phenolic compounds. We finally employed MTT-based cell viability protocol to assess the effects of crude EVOO phenolic extracts (PEs) on the metabolic status of cultured SKBR3 human breast cancer cells. MTT-based cell viability assays revealed a wide range of breast cancer cytotoxic potencies among individual crude PE obtained from EVOO monovarietals. Remarkably, breast cancer cell sensitivity to crude EVOO-PEs was up to 12 times higher in secoiridoids enriched-PE than in secoiridoids-low/null EVOO-PE.

Extra Virgin Olive Oil Components and Oxidative Stability from Olives Grown in Tunisia (Journal of the american oil chemits’ society, Vol 87 (10), pp 1199-1209)

Abstract:

The effects of the contents of lipids, pigments, ?-tocopherol and phenols were studied in relation to the antioxidant capacity of five virgin olive oils obtained from five olive cultivars planted in Tunisia (Arbequina, Koroneiki, Leccino, Oueslati and Chemchali). The antioxidant capacities were evaluated by two different radical scavenging activities: radical scavenging activity by the DPPH assay (RSA-DPPH) and total antioxidant status by the ABTS test (TAA-ABTS). The highest contents of antioxidant compounds (75.96, 10.34, 6.32, 15.39 and 241.52 mg kg-1 for oleic acid, O/L ratio, carotenes, chlorophylls and total phenols, respectively) were found for the Koroneiki cultivar except for a-tocopherol and o-diphenols, which had the highest contents (369 and 160.7 mg kg-1, respectively) in the Leccino and Chemchali cultivars (cvs). Furthermore, the highest antioxidant capacity in virgin olive oil was observed in the Koroneiki cultivar (0.24 mmol TE kg-1) followed by the Chemchali and Leccino cvs (0.22 and 0.13 mmol TE kg -1) for the TAA-ABTS test. However, the RSA-DPPH activity was higher for the Chemchali cultivar (19.9%) than for the Koroneiki and Leccino cvs (18.4 and 13.5%, respectively). Correlation between these capacities and the oil composition revealed that they were mainly influenced by the carotene content, followed by chlorophyll and phenolic contents where the ABTS test was more pronounced. Then, the antioxidant capacity of the virgin olive oils was correlated with polar components and the lipid profile which are important for its shelf life. © AOCS 2010.

Existen más publicaciones recientes de temas relacionados con aceite y salud. Si estáis interesados, no dudéis en contactar con nosotros y os daremos toda la información que esté a nuestro alcance.

Porque no todos los alimentos funcionales son procesados, aquí una muestra de los beneficios de nuestro oro líquido.

Nos complace compartir con vosotros el premio que recibieron los investigadores del CIDAF por su estudio sobre aceite de oliva y salud.

El título del proyecto es:

Extra Virgin Olive Oil Polyphenols: a natural source of new epigenetic drugs against breast cancer

(Polifenoles del Aceite de Oliva Virgen Extra: Una Fuente Natural de Nuevos Fármacos Epigenéticos contra el Cáncer de Mama)

ABSTRACT

We have employed high-throughput techniques to identify the molecular biology behind the growth inhibitory effects of Extra Virgin Olive Oil (EVOO)-derived crude phenolic extracts (PE) against breast cancer (BC) cells naturally exhibiting de novo cross-resistance to moleculartargeted drugs. EVOO PE-induced BC cell growth inhibition positively correlated with a higher presence of the complex polyphenols secoiridoids instead of lignans. The use of Agilent’s whole human genome arrays followed by GSEA-based screening of the KEGG pathway database revealed a differential modulation of the BC transcriptome at the level of the cell cycle & p53 pathways. EVOO PE differentially impacted the expression status of stress-sensing, G2-M checkpoint-related GADD45 genes and of p53-related CDKN1ACDKN1C, andPMAIP-1 genes. Cell cycle and fluorescence microscopy analyses confirmed that secoiridoids-rich EVOO PE inhibited mitosis to promote G2-M cell cycle arrest. This was accompanied with the appearance of diffuse, even, DNA staining with g-H2AX and pan-nuclear hyperacetylation of Histone H3 at Lysine 18. Secoiridoids-rich EVOO PE differentially hyperactivated p38 MAPK, a GADD45-related kinase involved in Histone H3 acetylation. Oleaceae secoiridoids appear to permit histones to remain in hyperacetylated states and through the resulting alterations in gene regulation to reduce mitotic viability and metabolic competence of human breast cancer cells.

En el centro se está llevando a cabo un estudio exhaustivo referente a todo lo que concierne al aceite de oliva, desde la caracterización de diversas variedades nacionales e internacionales, así como el estudio de las mismas y su potencial efecto beneficioso sobre la salud.

Así, algunos de los estudios más recientes llevados a cabo en estos dos últimos años se muestran a continuación:

Wastes Generated during the Storage of Extra Virgin Olive Oil as a Natural Source of Phenolic Compounds. (J. Agric. Food Chem, 2011, 59 (21), pp 11491-11500)

Abstract:

Phenolic compounds in extra virgin olive oil (EVOO) have been associated with beneficial effects for health. Indeed, these compounds exert strong antiproliferative effects on many pathological processes, which has stimulated chemical characterization of the large quantities of wastes generated during olive oil production. In this investigation, the potential of byproducts generated during storage of EVOO as a natural source of antioxidant compounds has been evaluated using solid–liquid and liquid–liquid extraction processes followed by rapid resolution liquid chromatography (RRLC) coupled to electrospray time-of-flight and ion trap mass spectrometry (TOF/IT-MS). These wastes contain polyphenols belonging to different classes such as phenolic acids and alcohols, secoiridoids, lignans, and flavones. The relationship between phenolic and derived compounds has been tentatively established on the basis of proposed degradation pathways. Finally, qualitative and quantitative characterizations of solid and aqueous wastes suggest that these byproducts can be considered an important natural source of phenolic compounds, mainly hydroxytyrosol, tyrosol, decarboxymethyl oleuropein aglycone, and luteolin, which, after suitable purification, could be used as food antioxidants or as ingredients in nutraceutical products due to their interesting technological and pharmaceutical properties.

Crude phenolic extracts from extra virgin olive oil circumvent de novo breast cancer resistance to HER1/HER2-targeting drugs by inducing GADD45-sensed cellular stress, G2/M arrest and hyperacetylation of Histone H3(International Journal of Oncology, 38 (6), pp 1533-1547)

Abstract:

Characterization of the molecular function of complex phenols naturally present in extra virgin olive oil (EVOO) against the HER2-gene amplified JIMT-1 cell line, a unique breast cancer model that inherently exhibits cross-resistance to multiple HER1/2-targeted drugs including trastuzumab, gefitinib, erlotinib and lapatinib, may underscore innovative cancer molecules with novel therapeutic targets because they should efficiently circumvent de novo resistance to HER1/2 inhibitors in order to elicit tumoricidal effects. We identified pivotal signaling pathways associated with the efficacy of crude phenolic extracts (PEs) obtained from 14 monovarietals of Spanish EVOOs. i) MTT-based cell viability and HPLC coupled to time-of-flight (TOF) mass spectrometry assays revealed that anti-cancer activity of EVOO PEs positively correlated with the phenolic index (i.e., total content of phenolics) and with a higher presence of the complex polyphenols secoiridoids instead of lignans. ii) Genome-wide analyses using 44 K Agilent’s whole human arrays followed by Gene Set Enrichment Analysis (GSEA)-based screening of the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database revealed a differential modulation of the JIMT-1 transcriptome at the level of the cell cycle and p53 pathways. EVOO PEs differentially impacted the expression status of stress-sensing, G2-M check-point-related GADD45 genes and of p53-related CDKN1A, CDKN1C and PMAIP-1 genes. iii) Cell cycle and fluorescence microscopy analyses confirmed that secoiridoid-rich EVOO PE inhibited mitosis to promote G2-M cell cycle arrest. This was accompanied with the appearance of diffuse, even DNA staining with γH2AX and pan-nuclear hyperacetylation of Histone H3 at Lysine 18. iv) Semi-quantitative Signaling Node Multi-Target ELISAs determined that secoiridoid-rich EVOO PE drastically activated the mitogen-activated protein kinases MEK1 and p38 MAPK, a GADD45-related kinase involved in Histone H3 acetylation. Secoiridoids, a family of complex polyphenols characteristic of Oleaceae plants, appear to permit histones to remain in hyperacetylated states and through the resulting alterations in gene regulation to reduce mitotic viability and metabolic competence of breast cancer cells inherently refractory to HER-targeting therapies ab initio. Oleaceae secoiridoids could provide a valuable phytochemical platform for the design of more pharmacologically active second-generation phytopharmaceutical anti-breast cancer molecules with a unique mode of action.

Prediction of Extra Virgin Olive Oil Varieties through Their Phenolic Profile. Potential Cytotoxic Activity against Human Breast Cancer Cells. (J. Agric. Food Chem, 2010, 58 (18), pp 9942-9955)

Abstract:

The aim of this work was to develop a rapid resolution liquid chromatography coupled to electrospray ionization time-of-flight mass spectrometry (RRLC-ESI-TOF-MS) method followed by tetrazolium salt (MTT)-based cell viability assays for qualitative and quantitative classification of extra virgin olive oil (EVOO) varieties by phenolic and other polar compound contents as well as for rapid characterization of putative cytotoxic activities against human cancer cells. Five different Spanish EVOO varieties were analyzed, and RRLC-ESI-TOF-MS method was applied for qualitative and quantitative identification of most important phenolic compounds. We finally employed MTT-based cell viability protocol to assess the effects of crude EVOO phenolic extracts (PEs) on the metabolic status of cultured SKBR3 human breast cancer cells. MTT-based cell viability assays revealed a wide range of breast cancer cytotoxic potencies among individual crude PE obtained from EVOO monovarietals. Remarkably, breast cancer cell sensitivity to crude EVOO-PEs was up to 12 times higher in secoiridoids enriched-PE than in secoiridoids-low/null EVOO-PE.

Extra Virgin Olive Oil Components and Oxidative Stability from Olives Grown in Tunisia (Journal of the american oil chemits’ society, Vol 87 (10), pp 1199-1209)

Abstract:

The effects of the contents of lipids, pigments, ?-tocopherol and phenols were studied in relation to the antioxidant capacity of five virgin olive oils obtained from five olive cultivars planted in Tunisia (Arbequina, Koroneiki, Leccino, Oueslati and Chemchali). The antioxidant capacities were evaluated by two different radical scavenging activities: radical scavenging activity by the DPPH assay (RSA-DPPH) and total antioxidant status by the ABTS test (TAA-ABTS). The highest contents of antioxidant compounds (75.96, 10.34, 6.32, 15.39 and 241.52 mg kg-1 for oleic acid, O/L ratio, carotenes, chlorophylls and total phenols, respectively) were found for the Koroneiki cultivar except for a-tocopherol and o-diphenols, which had the highest contents (369 and 160.7 mg kg-1, respectively) in the Leccino and Chemchali cultivars (cvs). Furthermore, the highest antioxidant capacity in virgin olive oil was observed in the Koroneiki cultivar (0.24 mmol TE kg-1) followed by the Chemchali and Leccino cvs (0.22 and 0.13 mmol TE kg -1) for the TAA-ABTS test. However, the RSA-DPPH activity was higher for the Chemchali cultivar (19.9%) than for the Koroneiki and Leccino cvs (18.4 and 13.5%, respectively). Correlation between these capacities and the oil composition revealed that they were mainly influenced by the carotene content, followed by chlorophyll and phenolic contents where the ABTS test was more pronounced. Then, the antioxidant capacity of the virgin olive oils was correlated with polar components and the lipid profile which are important for its shelf life. © AOCS 2010.

Existen más publicaciones recientes de temas relacionados con aceite y salud. Si estáis interesados, no dudéis en contactar con nosotros y os daremos toda la información que esté a nuestro alcance.