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      The Role of Natural Polyphenols in the Prevention and Treatment of Cervical Cancer—An Overview

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          Abstract

          Cervical cancer represents the second leading cause of death for women worldwide. The importance of the diet and its impact on specific types of neoplasia has been highlighted, focusing again interest in the analysis of dietary phytochemicals. Polyphenols have shown a wide range of cellular effects: they may prevent carcinogens from reaching the targeted sites, support detoxification of reactive molecules, improve the elimination of transformed cells, increase the immune surveillance and the most important factor is that they can influence tumor suppressors and inhibit cellular proliferation, interfering in this way with the steps of carcinogenesis. From the studies reviewed in this paper, it is clear that certain dietary polyphenols hold great potential in the prevention and therapy of cervical cancer, because they interfere in carcinogenesis (in the initiation, development and progression) by modulating the critical processes of cellular proliferation, differentiation, apoptosis, angiogenesis and metastasis. Specifically, polyphenols inhibit the proliferation of HPV cells, through induction of apoptosis, growth arrest, inhibition of DNA synthesis and modulation of signal transduction pathways. The effects of combinations of polyphenols with chemotherapy and radiotherapy used in the treatment of cervical cancer showed results in the resistance of cervical tumor cells to chemo- and radiotherapy, one of the main problems in the treatment of cervical neoplasia that can lead to failure of the treatment because of the decreased efficiency of the therapy.

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          Most cited references181

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          Flavonoids as antioxidants.

          Flavonoids are phenolic substances isolated from a wide range of vascular plants, with over 8000 individual compounds known. They act in plants as antioxidants, antimicrobials, photoreceptors, visual attractors, feeding repellants, and for light screening. Many studies have suggested that flavonoids exhibit biological activities, including antiallergenic, antiviral, antiinflammatory, and vasodilating actions. However, most interest has been devoted to the antioxidant activity of flavonoids, which is due to their ability to reduce free radical formation and to scavenge free radicals. The capacity of flavonoids to act as antioxidants in vitro has been the subject of several studies in the past years, and important structure-activity relationships of the antioxidant activity have been established. The antioxidant efficacy of flavonoids in vivo is less documented, presumably because of the limited knowledge on their uptake in humans. Most ingested flavonoids are extensively degraded to various phenolic acids, some of which still possess a radical-scavenging ability. Both the absorbed flavonoids and their metabolites may display an in vivo antioxidant activity, which is evidenced experimentally by the increase of the plasma antioxidant status, the sparing effect on vitamin E of erythrocyte membranes and low-density lipoproteins, and the preservation of erythrocyte membrane polyunsaturated fatty acids. This review presents the current knowledge on structural aspects and in vitro antioxidant capacity of most common flavonoids as well as in vivo antioxidant activity and effects on endogenous antioxidants.
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            The effects of plant flavonoids on mammalian cells: implications for inflammation, heart disease, and cancer.

            Flavonoids are nearly ubiquitous in plants and are recognized as the pigments responsible for the colors of leaves, especially in autumn. They are rich in seeds, citrus fruits, olive oil, tea, and red wine. They are low molecular weight compounds composed of a three-ring structure with various substitutions. This basic structure is shared by tocopherols (vitamin E). Flavonoids can be subdivided according to the presence of an oxy group at position 4, a double bond between carbon atoms 2 and 3, or a hydroxyl group in position 3 of the C (middle) ring. These characteristics appear to also be required for best activity, especially antioxidant and antiproliferative, in the systems studied. The particular hydroxylation pattern of the B ring of the flavonoles increases their activities, especially in inhibition of mast cell secretion. Certain plants and spices containing flavonoids have been used for thousands of years in traditional Eastern medicine. In spite of the voluminous literature available, however, Western medicine has not yet used flavonoids therapeutically, even though their safety record is exceptional. Suggestions are made where such possibilities may be worth pursuing.
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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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                Author and article information

                Contributors
                Role: Academic Editor
                Role: Academic Editor
                Journal
                Molecules
                Molecules
                molecules
                Molecules
                MDPI
                1420-3049
                17 August 2016
                August 2016
                : 21
                : 8
                : 1055
                Affiliations
                [1 ]Department of Medical and Surgical Specialties, Faculty of Medicine, Transilvania University of Brasov, Brasov 500019, Romania; moga.og@ 123456gmail.com (M.A.M.); dimienescu.oana@ 123456gmail.com (O.G.D.); cristiarv@ 123456yahoo.com (C.A.A.); aurel.mironescu@ 123456gmail.com (A.M.)
                [2 ]Clinical Department of Obstetrics and Gynecology, The Carol Davila University of Medicine and Pharmacy, Bucharest 020021, Romania; liaples@ 123456yahoo.com
                Author notes
                [* ]Correspondence: dracea.laura@ 123456yahoo.com ; Tel.: +40-422-6841-2185
                Article
                molecules-21-01055
                10.3390/molecules21081055
                6274328
                27548122
                93e661d0-eedc-4aba-9b9e-aa842069f97b
                © 2016 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 (CC-BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 30 June 2016
                : 08 August 2016
                Categories
                Review

                natural polyphenols,cervical cancer,carcinogenesis,bioavailability,chemotherapy

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