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      Selecting bioactive phenolic compounds as potential agents to inhibit proliferation and VEGF expression in human ovarian cancer cells

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          Abstract

          Ovarian cancer is a disease that continues to cause mortality in female individuals worldwide. Ovarian cancer is challenging to treat due to emerging resistance to chemotherapy, therefore, the identification of effective novel chemotherapeutic agents is important. Polyphenols have demonstrated potential in reducing the risk of developing numerous types of cancer, as well reducing the risk of cancer progression, due to their ability to reduce cell viability and vascular endothelial growth factor (VEGF) expression. In the present study, eight phenolic compounds were screened in two human ovarian cancer cell lines (OVCAR-3 and A2780/CP70) to determine their effect on proliferation suppression and VEGF protein secretion inhibition, in comparison to cisplatin, a conventional chemotherapeutic agent. The current study identified that 40 μM gallic acid (GA) exhibited the greatest inhibitory effect on OVCAR-3 cell viability, compared with all of the phenolic compounds investigated. Similarly to cisplatin, baicalein, GA, nobiletin, tangeretin and baicalin were all identified to exhibit significant VEGF inhibitory effects from ELISA results. Furthermore, western blot analysis indicated that GA effectively decreased the level of the VEGF-binding protein hypoxia-inducible factor-1α in the ovarian cancer cell line. Considering the results of the present study, GA appears to inhibit cell proliferation and, thus, is a potential agent for the treatment of ovarian cancer.

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          Chemopreventive effects of dietary phytochemicals against cancer invasion and metastasis: phenolic acids, monophenol, polyphenol, and their derivatives.

          Cancer metastasis is the major cause of cancer-related death, and chemoprevention is defined as the use of natural or synthetic substances to prevent cancer formation or cancer progress. Evidence that phenolic compounds may have a potential inhibitory effect on cancer invasion and metastasis is increasingly being reported in the scientific literature. Curcumin, resveratrol, and their related derivatives are the most studied compounds in this topic so far; gallic acid, chlorogenic acid, caffeic acid, carnosol, capsaicin, 6-shogaol, 6-gingerol, and their corresponding derivatives are also suggested to be the active members of the phenolic family on anti-invasion and anti-metastasis. Because metastasis occurs through a multistep process, these bioactives might act on a variety of stages of the metastatic process to prevent tumor cells from metastasizing. This review summarizes the common protein targets and signaling pathways for the inhibition of invasion and metastasis as well as past publications on the in vitro and in vivo effects and molecular mechanisms of phenolic acids, monophenol, polyphenol, and their derivatives, except flavonoids, on cancer invasion and metastasis. Based on these data, we conclude that the daily consumption of natural dietary components that are rich in phenolics could be beneficial for the prevention of cancer metastasis. 2011 Elsevier Ltd. All rights reserved.
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            Cancer chemoprevention by dietary polyphenols: promising role for epigenetics.

            Epigenetics refers to heritable changes that are not encoded in the DNA sequence itself, but play an important role in the control of gene expression. In mammals, epigenetic mechanisms include changes in DNA methylation, histone modifications and non-coding RNAs. Although epigenetic changes are heritable in somatic cells, these modifications are also potentially reversible, which makes them attractive and promising avenues for tailoring cancer preventive and therapeutic strategies. Burgeoning evidence in the last decade has provided unprecedented clues that diet and environmental factors directly influence epigenetic mechanisms in humans. Dietary polyphenols from green tea, turmeric, soybeans, broccoli and others have shown to possess multiple cell-regulatory activities within cancer cells. More recently, we have begun to understand that some of the dietary polyphenols may exert their chemopreventive effects in part by modulating various components of the epigenetic machinery in humans. In this article, we first discuss the contribution of diet and environmental factors on epigenetic alterations; subsequently, we provide a comprehensive review of literature on the role of various dietary polyphenols. In particular, we summarize the current knowledge on a large number of dietary agents and their effects on DNA methylation, histone modifications and regulation of expression of the non-coding miRNAs in various in vitro and in vivo models. We emphasize how increased understanding of the chemopreventive effects of dietary polyphenols on specific epigenetic alterations may provide unique and yet unexplored novel and highly effective chemopreventive strategies for reducing the health burden of cancer and other diseases in humans. Copyright © 2010 Elsevier Inc. All rights reserved.
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              Chemopreventive effect of dietary polyphenols in colorectal cancer cell lines.

              Colorectal cancer (CRC) is the second most fatal and the third most diagnosed type of cancer worldwide. Despite having multifactorial causes, most CRC cases are mainly determined by dietary factors. In recent years, a large number of studies have attributed a protective effect to polyphenols and foods containing these compounds (fruits and vegetables) against CRC. Indeed, polyphenols have been reported to interfere with cancer initiation, promotion, and progression, acting as chemopreventive agents. The aim of this review is to summarize the main chemopreventive properties of some polyphenols (quercetin, rutin, myricetin, chrysin, epigallocatechin-3-gallate, epicatechin, catechin, resveratrol, and xanthohumol) against CRC, observed in cell culture models. From the data reviewed in this article, it can be concluded that these compounds inhibit cell growth, by inducing cell cycle arrest and/or apoptosis; inhibit proliferation, angiogenesis, and/or metastasis; and exhibit anti-inflammatory and/or antioxidant effects. In turn, these effects involve multiple molecular and biochemical mechanisms of action, which are still not completely characterized. Thus, caution is mandatory when attempting to extrapolate the observations obtained in CRC cell line studies to humans. Copyright © 2011 Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                Oncol Lett
                Oncol Lett
                OL
                Oncology Letters
                D.A. Spandidos
                1792-1074
                1792-1082
                March 2015
                22 December 2014
                22 December 2014
                : 9
                : 3
                : 1444-1450
                Affiliations
                [1 ]Key Laboratory for Quality Improvement of Agricultural Products of Zhejiang Province, College of Agriculure and Food Science, Zhejiang A & F University, Lin’an, Zhejiang 311300, P.R. China
                [2 ]College of Science, Technology and Mathematics, Alderson Broaddus University, Philippi, WV 26416, USA
                [3 ]Department of Pharmacology, Physiology and Toxicology, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25701, USA
                [4 ]Department of Basic Pharmaceutical Science, West Virginia University, Morgantown, WV 26506, USA
                Author notes
                Correspondence to: Dr Yi Charlie Chen, College of Science, Technology and Mathematics, Alderson Broaddus University, 101 College Hill, Philippi, WV 26416, USA, E-mail: chenyc@ 123456ab.edu
                Article
                ol-09-03-1444
                10.3892/ol.2014.2818
                4314987
                25663929
                8fa8e837-e4b0-4b59-bdab-f82a2a5a2ad9
                Copyright © 2015, Spandidos Publications

                This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.

                History
                : 14 April 2014
                : 02 December 2014
                Categories
                Articles

                Oncology & Radiotherapy
                phenolic compound,ovarian cancer,cell viability,vascular endothelial growth factor,hypoxia-inducible factor-1α

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