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      Dietary phytochemicals and cancer chemoprevention: a review of the clinical evidence

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          Abstract

          Cancer chemoprevention involves the use of different natural or biologic agents to inhibit or reverse tumor growth. Epidemiological and pre-clinical data suggest that various natural phytochemicals and dietary compounds possess chemopreventive properties, and in-vitro and animal studies support that these compounds may modulate signaling pathways involved in cell proliferation and apoptosis in transformed cells, enhance the host immune system and sensitize malignant cells to cytotoxic agents. Despite promising results from experimental studies, only a limited number of these compounds have been tested in clinical trials and have shown variable results. In this review, we summarize the data regarding select phytochemicals including curcumin, resveratrol, lycopene, folates and tea polyphenols with emphasis on the clinical evidence supporting the efficacy of these compounds in high-risk populations.

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          Most cited references99

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          Cancer chemoprevention with dietary phytochemicals.

          Chemoprevention refers to the use of agents to inhibit, reverse or retard tumorigenesis. Numerous phytochemicals derived from edible plants have been reported to interfere with a specific stage of the carcinogenic process. Many mechanisms have been shown to account for the anticarcinogenic actions of dietary constituents, but attention has recently been focused on intracellular-signalling cascades as common molecular targets for various chemopreventive phytochemicals.
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            Oxidative stress and cancer: an overview.

            Reactive species, which mainly include reactive oxygen species (ROS), are products generated as a consequence of metabolic reactions in the mitochondria of eukaryotic cells. In normal cells, low-level concentrations of these compounds are required for signal transduction before their elimination. However, cancer cells, which exhibit an accelerated metabolism, demand high ROS concentrations to maintain their high proliferation rate. Different ways of developing ROS resistance include the execution of alternative pathways, which can avoid large amounts of ROS accumulation without compromising the energy demand required by cancer cells. Examples of these processes include the guidance of the glycolytic pathway into the pentose phosphate pathway (PPP) and/or the generation of lactate instead of employing aerobic respiration in the mitochondria. Importantly, ROS levels can be used as a thermostat to monitor the damage that cells can bear. The implications for ROS regulation are highly significant for cancer therapy because commonly used radio- and chemotherapeutic drugs influence tumor outcome through ROS modulation. Moreover, the discovery of novel biomarkers that are able to predict the clinical response to pro-oxidant therapies is a crucial challenge to overcome to allow for the personalization of cancer therapies. Copyright © 2012 Elsevier B.V. All rights reserved.
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              NKG2D-deficient mice are defective in tumor surveillance in models of spontaneous malignancy.

              Ligands for the NKG2D stimulatory receptor are frequently upregulated on tumor lines, rendering them sensitive to natural killer (NK) cells, but the role of NKG2D in tumor surveillance has not been addressed in spontaneous cancer models. Here, we provided the first characterization of NKG2D-deficient mice, including evidence that NKG2D was not necessary for NK cell development but was critical for immunosurveillance of epithelial and lymphoid malignancies in two transgenic models of de novo tumorigenesis. In both models, we detected NKG2D ligands on the tumor cell surface ex vivo, providing needed evidence for ligand expression by primary tumors. In a prostate cancer model, aggressive tumors arising in NKG2D-deficient mice expressed higher amounts of NKG2D ligands than did similar tumors in wild-type mice, suggesting an NKG2D-dependent immunoediting of tumors in this model. These findings provide important genetic evidence for surveillance of primary tumors by an NK receptor.
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                Author and article information

                Journal
                Oncotarget
                Oncotarget
                Oncotarget
                ImpactJ
                Oncotarget
                Impact Journals LLC
                1949-2553
                9 August 2016
                24 May 2016
                : 7
                : 32
                : 52517-52529
                Affiliations
                1 Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, United States of America
                2 Department of Internal Medicine, Division of Hematology, Aichi Medical University, School of Medicine, Nagakute, Aichi, Japan
                3 Department of Hematology Oncology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan
                Author notes
                Correspondence to: J. Luis Espinoza, luis@ 123456staff.kanazawa-u.ac.jp
                Article
                9593
                10.18632/oncotarget.9593
                5239570
                27232756
                d7cad7fb-d588-42cc-883a-057d1eb3d878
                Copyright: © 2016 Kotecha et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 30 December 2015
                : 12 May 2016
                Categories
                Review

                Oncology & Radiotherapy
                cancer chemoprevention,phytochemicals,resveratrol,curcumin,antioxidants
                Oncology & Radiotherapy
                cancer chemoprevention, phytochemicals, resveratrol, curcumin, antioxidants

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