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Highlights <http://www.sciencedirect.com/science/article/pii/S0925443911002286> * Keywords <http://www.sciencedirect.com/science/article/pii/S0925443911002286> * 1. Introduction: cervical cancer <http://www.sciencedirect.com/science/article/pii/S0925443911002286> * 2. HPV: structure, infection and transformation activity <http://www.sciencedirect.com/science/article/pii/S0925443911002286> * 3. Oxidative stress and cervical cancer <http://www.sciencedirect.com/science/article/pii/S0925443911002286> * 4. Antioxidants, chemoprevention and chemotherapy <http://www.sciencedirect.com/science/article/pii/S0925443911002286> * 5. Polyphenols and cervical cancer <http://www.sciencedirect.com/science/article/pii/S0925443911002286> * <#f0005> * <#f0010> * 5.1. Curcumin and ferulic acid <http://www.sciencedirect.com/science/article/pii/S0925443911002286> * Table 1 <#t0005> * 5.2. Epigallocatechin-3-gallate <http://www.sciencedirect.com/science/article/pii/S0925443911002286> * 5.3. Resveratrol <http://www.sciencedirect.com/science/article/pii/S0925443911002286> * 6. Clinical trial in cervical cancer <http://www.sciencedirect.com/science/article/pii/S0925443911002286> * 7. Conclusions <http://www.sciencedirect.com/science/article/pii/S0925443911002286> * References <http://www.sciencedirect.com/science/article/pii/S0925443911002286> Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease <http://www.sciencedirect.com/science/journal/09254439> Volume 1822, Issue 5 <http://www.sciencedirect.com/science/journal/09254439/1822/5>, May 2012, Pages 737747 Antioxidants and Antioxidant Treatment in Disease Edited By D.A. Butterfield and J.N. Keller Cover image <http://www.sciencedirect.com/science/journal/09254439/1822/5> Review

Antioxidants in cervical cancer: Chemopreventive and chemotherapeutic effects of polyphenols ^ <#item1> * * * * F. Di Domenico <#>^a <#af0005>, C. Foppoli <#>^b <#af0010>, R. Coccia <#>^a <#af0005>, M. Perluigi <#>^a <#af0005>^, Corresponding author contact information <#cr0005>^, E-mail the corresponding author <mailto:marzia.perluigi@uniroma1.it>

* ^a Department of Biochemical Sciences, Sapienza University of Rome, P.le A. Moro, 5-00185 Rome, Italy * ^b CNR Institute of Molecular Biology and Pathology, Sapienza University of Rome, Rome, Italy ^Corresponding author contact information <#bcr0005> Corresponding author. Tel.: + 39 0649910900. Received 27 August 2011 Revised 5 October 2011 Accepted 6 October 2011 Available online 12 October 2011 * http://dx.doi.org/10.1016/j.bbadis.2011.10.005, How to Cite or Link Using DOI <http://www.sciencedirect.com/science/help/doi.htm> * Permissions & Reprints </science?_ob=RedirectURL&_method=outwardLink&_partnerName=936&_eid=1-s2.0-S 0925443911002286&_pii=S0925443911002286&_origin=article&_zone=art_page&_targetUR L=https%3A%2F%2Fs100.copyright.com%2FAppDispatchServlet%3FpublisherName%3DELS%26 contentID%3DS0925443911002286%26orderBeanReset%3Dtrue&_acct=C000228598&_version= 1&_userid=10&md5=6653f077a24694977086189b3e06dbfd> View full text <http://www.sciencedirect.com/science/article/pii/S0925443911002286> Purchase $31.50 </science?_ob=ShoppingCartURL&_method=add&_eid=1-s2.0-S0925443911002286&_acct=C 000228598&_version=1&_userid=10&_ts=1360870153&md5=eb5543e01f110b0946ed888373d11 d39> <http://www.deepdyve.com/lp/elsevier/antioxidants-in-cervical-cancer-chemopreven tive-and-chemotherapeutic-3evfHFfGGs?key=elsevier>

1. Introduction: cervical cancer 2. HPV: structure, infection and transformation activity 3. Oxidative stress and cervical cancer 4. Antioxidants, chemoprevention and chemotherapy 5. Polyphenols and cervical cancer

6. Clinical trial in cervical cancer 7. Conclusions References -----------------------------------------------------------------------Abstract Cervical cancer lesions are a major threat to the health of women, representing the second most common cancer worldwide. The unanimously recognized etiological factor in the causation of cervical cancer is the infection with human papilloma virus (HPV). HPV infection, although necessary, is not /per se/ sufficient to induce cancer. Other factors have to be involved in the progression of infected cells to the full neoplastic phenotype. Oxidative stress represents an interesting and under-explored candidate as a promoting factor in HPV-initiated carcinogenesis. Oxidative stress is known to perturb the cellular redox status thus leading to alteration of gene expression responses through the activation of several redox-sensitive transcription factors. This signaling cascade affects both cell growth and cell death. The ability of naturally occurring antioxidants to modulate cellular signal transduction pathways, through the activation/repression of multiple redox-sensitive transcription factors, has been claimed for their potential therapeutic use as chemopreventive agents. Among these compounds, polyphenols have been found to be promising agents toward cervical cancer. In addition to acting as antioxidants, polyphenols display a wide variety of biological function including induction of apoptosis, growth arrest, inhibition of DNA synthesis and modulation of signal transduction pathways. They can interfere with each stage of carcinogenesis initiation, promotion and progression to prevent cancer development. The present review discusses current knowledge of the major molecular pathways, which are involved in HPV-driven cancerogenesis, and the ability of polyphenols to modulate these pathways. By acting at specific steps of viral transformation cascade, polyphenols have been demonstrated to selectively inhibit tumor cell growth and may be a promising therapeutic tool for treatment of cervical cancer. In addition, recent results obtained in clinical trials using polyphenols are also discussed. This article is part of a Special Issue entitled: Antioxidants and Antioxidant Treatment in Disease. -----------------------------------------------------------------------Highlights Cervical cancer is the second most common cancer among women worldwide and represents a major concern for public health. Oxidative stress is a candidate factor involved in the pathogenesis and progression of cervical cancer. Polyphenols have been found to be promising agents toward cervical cancer. In addition to act as antioxidants, polyphenols display a wide variety of biological functions. Polyphenols were demonstrated to inhibit the proliferation of HPV-positive cancer cells.

Keywords * * * * * Cervical cancer; HPV; Polyphenol; Apoptosis; Oxidative stress

-----------------------------------------------------------------------Figures and tables from this article: Full-size image (108 K) <#gr1> Fig. 1. Molecular mechanisms of human papillomavirus-induced carcinogenesis. Oncogenic action of high-risk HPV E6 and E7 oncoproteins is exerted through the inactivation of tumor suppressors p53 and pRb, respectively. Abrogation of p53 by E6 ensures cell survival by preventing apoptosis inactivation while pRb inactivation by E7 forces infected cells to remain in a proliferative state. The dark red box represent the target of action of the polyphenols considered: C = curcumin; E = EGCG; R = resveratrol. Figure options <#> * View in workspace <#f0005> Full-size image (62 K) <#gr2> Fig. 2. Polyphenolic antioxidants. Chemical structure, properties and sources of curcumin (1,7-bis (4-hydroxy 3-methoxy phenyl)-1,6-heptadiene-3,5-dione), ferulic acid (3-methoxy-4-hydroxycinnamic acid), EGCG (epigallocatechin-3-gallate) and resveratrol (/trans/-3,5,4-trihydroxy-/trans/-stilbene). Figure options <#> * View in workspace <#f0010> Table 1. Biochemical effects and molecular targets of chemopreventive action of polyphenols (curcumin, ferulic acid, EGCG, and resveratrol) in cervical cancer models. View Within Article </science/article/pii/S0925443911002286> <#bitem1> This article is part of a Special Issue entitled: Antioxidants and Antioxidant Treatment in Disease. ^Corresponding author contact information <#bcr0005> Corresponding author. Tel.: + 39 0649910900. Copyright 2011 Elsevier B.V. All rights reserved. Bibliographic information

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