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      Oleanolic Acid, a Compound Present in Grapes and Olives, Protects against Genotoxicity in Human Mammary Epithelial Cells

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          Abstract

          Oleanolic acid (AO) and maslinic acid (MA) are constituents of the skins of different fruits, including olives and white or red grapes. Although both compounds are known to have beneficial properties against different types of cancers, thus far, there are no studies about their chemopreventive effects in human breast cancer. Thus, we sought to elucidate whether both compounds possess chemopreventive activity. Two cell lines of human breast cancer cells and one noncancerous human mammary epithelial cells were used to determine the effects of OA and MA. The results showed that OA inhibited the proliferation and increased the oxidative stress of highly invasive cells. Additionally, OA decreased oxidative stress and oxidative damage to the DNA in human mammary epithelial cells. These results suggest that OA could act as a chemopreventive agent in human breast cancer and could inhibit the proliferation of highly invasive breast cancer cells.

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          Maslinic acid, a natural triterpene from Olea europaea L., induces apoptosis in HT29 human colon-cancer cells via the mitochondrial apoptotic pathway.

          We have investigated the mechanisms of maslinic acid with regard to its inhibitory effects on the growth of HT29 colon-cancer cells. High concentrations of maslinic acid are present in the protective wax-like coating of olives. Our results show that treatment with maslinic acid results in a significant inhibition of cell proliferation in a dose-dependent manner and causes apoptotic death in colon-cancer cells. We found that it inhibits considerably the expression of Bcl-2 whilst increasing that of Bax; it also stimulates the release of mitochondrial cytochrome-c and activates caspase-9 and caspase-3. All these results point clearly to the activation of the mitochondrial apoptotic pathway in response to the treatment of HT29 colon-cancer cells with maslinic acid. Our results suggest that maslinic acid has the potential to provide significant natural defence against colon-cancer.
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            Hydroxytyrosol Protects against Oxidative DNA Damage in Human Breast Cells

            Over recent years, several studies have related olive oil ingestion to a low incidence of several diseases, including breast cancer. Hydroxytyrosol and tyrosol are two of the major phenols present in virgin olive oils. Despite the fact that they have been linked to cancer prevention, there is no evidence that clarifies their effect in human breast tumor and non-tumor cells. In the present work, we present hydroxytyrosol and tyrosol’s effects in human breast cell lines. Our results show that hydroxytyrosol acts as a more efficient free radical scavenger than tyrosol, but both fail to affect cell proliferation rates, cell cycle profile or cell apoptosis in human mammary epithelial cells (MCF10A) or breast cancer cells (MDA-MB-231 and MCF7). We found that hydroxytyrosol decreases the intracellular reactive oxygen species (ROS) level in MCF10A cells but not in MCF7 or MDA-MB-231 cells while very high amounts of tyrosol is needed to decrease the ROS level in MCF10A cells. Interestingly, hydroxytyrosol prevents oxidative DNA damage in the three breast cell lines. Therefore, our data suggest that simple phenol hydroxytyrosol could contribute to a lower incidence of breast cancer in populations that consume virgin olive oil due to its antioxidant activity and its protection against oxidative DNA damage in mammary cells.
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              Squalene protects against oxidative DNA damage in MCF10A human mammary epithelial cells but not in MCF7 and MDA-MB-231 human breast cancer cells.

              Until now, very little has been known about the antioxidant capacity of squalene and its effect on human breast tumourigenesis. In the present work, we investigated squalene's scavenging properties and its effect on cell proliferation, cell cycle profile, apoptosis, reactive oxygen species (ROS) level and oxidative DNA damage, using human breast cell lines. Our results showed that squalene neither possesses scavenging activity nor significantly alters cell proliferation rates, the cell cycle profile or cell apoptosis in human mammary epithelial cells (MCF10A), minimally invasive (MDA-MB-231) breast cancer cells, and highly invasive (MCF7) breast cancer cells. However, we found that squalene did exert the following effects on MCF10A epithelial cells in a dose-dependent manner: (a) it decreased intracellular ROS level, (b) it prevented H(2)O(2)-induced oxidative injury, and (c) it protected against oxidative DNA damage. Interestingly, squalene did not exert these effects on MCF7 and MDA-MB-231 cancer cells. Therefore, our data suggest that squalene, found in high amounts in virgin olive oils, could be partially responsible for the lower incidence of breast cancer in populations that consume the Mediterranean diet due to its protective activity against oxidative DNA damage in normal mammary cells. 2010 Elsevier Ltd. All rights reserved.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Molecules
                Molecules
                molecules
                Molecules
                MDPI
                1420-3049
                28 July 2015
                August 2015
                : 20
                : 8
                : 13670-13688
                Affiliations
                [1 ]Immunology Division, Department of Health Sciences, Faculty of Experimental Sciences, University of Jaén, Campus las Lagunillas s/n, 23071 Jaén, Spain; E-Mails: csquesad@ 123456ujaen.es (C.S.-Q.); albiedma@ 123456ujaen.es (A.L.-B.)
                [2 ]Centro de Estudios Avanzados en Olivar y Aceites de Oliva, University of Jaén, Campus las Lagunillas s/n, 23071 Jaén, Spain
                [3 ]Agrifood Campus of International Excellence, ceiA3, University of Jaén, Campus las Lagunillas s/n, 23071 Jaén, Spain
                Author notes
                [* ]Author to whom correspondence should be addressed; E-Mail: jgaforio@ 123456ujaen.es ; Tel.: +34-953-212-193; Fax: +34-953-212-943.
                Article
                molecules-20-13670
                10.3390/molecules200813670
                6332039
                26225949
                ce2dabe5-6e09-45a5-8de3-b0108255119e
                © 2015 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 26 June 2015
                : 24 July 2015
                Categories
                Article

                virgin olive oil,wine,maslinic acid,mcf7,mda-mb-231,mcf10a,chemopreventive,antitumoral

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