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      Cytotoxic Effects of Strawberry, Korean Raspberry, and Mulberry Extracts on Human Ovarian Cancer A2780 Cells

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          Abstract

          Reactive oxygen species are tumorigenic by their ability to increase cell proliferation, survival, and cellular migration. The purpose of the present study was to compare the antioxidant activity and cytotoxic effects of 3 berry extracts (strawberry, Korean raspberry, and mulberry) in A2780 human ovarian carcinoma cells. Except for raspberry, the ethyl acetate or methylene chloride fractions of berries containing phenolic compounds exerted dose dependent free radical scavenging activities. In the raspberry fractions, the hexane fraction also exhibited potent antioxidant activity. The cytotoxic effects of berries extracts in A2780 human ovarian carcinoma cells were measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Surprisingly, co-treatment with n-butanol (BuOH) fractions of berries showed stronger cytotoxic effects compared to the other fractions. These findings suggest that potent anticancer molecules are found in the BuOH fractions of berries that have stronger cytotoxic activity than antioxidants.

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          Isolation and identification of strawberry phenolics with antioxidant and human cancer cell antiproliferative properties.

          Studies suggest that consumption of berry fruits, including strawberries ( Fragaria x ananassa Duch.), may have beneficial effects against oxidative stress mediated diseases such as cancer. Berries contain multiple phenolic compounds, which are thought to contribute to their biological properties. Comprehensive profiling of phenolics from strawberries was previously reported using high-performance liquid chromatography with mass spectrometry (HPLC-MS) detection. The current study reports the isolation and structural characterization of 10 phenolic compounds from strawberry extracts using a combination of Amberlite XAD16-resin and C18 columns, HPLC-UV, and nuclear magnetic resonance (NMR) spectroscopy methods. The phenolics were cyanidin-3-glucoside ( 1), pelargonidin (2), pelargonidin-3-glucoside (3), pelargonidin-3-rutinoside (4), kaempferol (5), quercetin (6), kaempferol-3-(6'-coumaroyl)glucoside) (7), 3,4,5-trihydroxyphenyl-acrylic acid (8), glucose ester of ( E)- p-coumaric acid (9), and ellagic acid . Strawberry crude extracts and purified compounds 1- 10 were evaluated for antioxidant and human cancer cell antiproliferative activities by the Trolox equivalent antioxidant capacity (TEAC) and luminescent ATP cell viability assays, respectively. Among the pure compounds, the anthocyanins 1 (7156 microM Trolox/mg), 2 (4922 microM Trolox/mg), and 4 (5514 microM Trolox/mg) were the most potent antioxidants. Crude extracts (250 microg/mL) and pure compounds (100 microg/mL) inhibited the growth of human oral (CAL-27, KB), colon (HT29, HCT-116), and prostate (LNCaP, DU145) cancer cells with different sensitivities observed between cell lines. This study adds to the growing body of data supporting the bioactivities of berry fruit phenolics and their potential impact on human health.
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            Role of antioxidants in cancer therapy.

            Oxidative stress is a key component in linking environmental toxicity to the multistage carcinogenic process. Reactive oxygen species (ROS) are generated in response to both endogenous and exogenous stimuli. To counterbalance ROS-mediated injury, an endogenous antioxidants defense system exists; however, when oxidation exceeds the control mechanisms, oxidative stress arises. Chronic and cumulative oxidative stress induces deleterious modifications to a variety of macromolecular components, such as DNA, lipids, and proteins. A primary mechanism of many chemotherapy drugs against cancer cells is the formation of ROS, or free radicals. Radiotherapy is based on the fact that ionizing radiation destroys tumor cells. Radiotherapy induces direct lesions in the DNA or biological molecules, which eventually affect DNA. Free radicals produced by oncology therapy are often a source of serious side effects as well. The objective of this review is to provide information about the effects of antioxidants during oncology treatments and to discuss the possible events and efficacy. Much debate has arisen about whether antioxidant supplementation alters the efficacy of cancer chemotherapy. There is still limited evidence in both quality and sample size, suggesting that certain antioxidant supplements may reduce adverse reactions and toxicities. Significant reductions in toxicity may alleviate dose-limiting toxicities so that more patients are able to complete prescribed chemotherapy regimens and thus, in turn, improve the potential for success in terms of tumor response and survival. Copyright © 2013 Elsevier Inc. All rights reserved.
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              Oxidative mechanisms in carcinogenesis.

              Cancer in humans and animals is a multistep disease process. In this process, a single cell can develop from an otherwise normal tissue into a malignancy that can eventually destroy the organism. The complex series of cellular and molecular changes that occur through the development of cancers can be mediated by a diversity of endogenous and environmental stimuli. Active oxygen species and other free radicals have long been known to be mutagenic; further, these agents have more recently emerged as mediators of the other phenotypic and genotypic changes that lead from mutation to neoplasia. Free radical production is ubiquitous in all respiring organisms, and is enhanced in many disease states, by carcinogen exposure, and under conditions of stress. Free radicals may therefore contribute widely to cancer development in humans. This review explores the molecular mechanisms through which free radicals can participate in the carcinogenic process.
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                Author and article information

                Journal
                Prev Nutr Food Sci
                Prev Nutr Food Sci
                Preventive Nutrition and Food Science
                The Korean Society of Food Science and Nutrition
                2287-1098
                2287-8602
                December 2016
                31 December 2016
                : 21
                : 4
                : 384-388
                Affiliations
                [1 ]Department of Food Science, Gyeongnam National University of Science and Technology, Gyeongnam 52725, Korea
                [2 ]College of Korean Medicine, Gachon University, Gyeonggi 13120, Korea
                [3 ]Department of Integrative Plant Science, Chung-Ang University, Gyeonggi 17546, Korea
                [4 ]Department of Food Science and Nutrition, Pusan National University, Busan 46241, Korea
                Author notes
                Correspondence to Hyun Young Kim, Tel: +82-55-751-3277, E-mail: hykim@ 123456gntech.ac.kr
                [*]

                These authors contributed equally to this work.

                Article
                pnfs-21-384
                10.3746/pnf.2016.21.4.384
                5216892
                9d82a360-519b-48c9-8527-22e57c2c6080
                Copyright © 2016 by The Korean Society of Food Science and Nutrition

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 27 September 2016
                : 29 November 2016
                Categories
                Research Note

                antioxidant,berry,ovarian cancer,cytotoxic effect
                antioxidant, berry, ovarian cancer, cytotoxic effect

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