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      Role of Apigenin in Cancer Prevention via the Induction of Apoptosis and Autophagy

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          Abstract

          Apigenin (4′,5,7-trihydroxyflavone) is a flavonoid commonly found in many fruits and vegetables such as parsley, chamomile, celery, and kumquats. In the last few decades, recognition of apigenin as a cancer chemopreventive agent has increased. Significant progress has been made in studying the chemopreventive aspects of apigenin both in vitro and in vivo. Several studies have demonstrated that the anticarcinogenic properties of apigenin occur through regulation of cellular response to oxidative stress and DNA damage, suppression of inflammation and angiogenesis, retardation of cell proliferation, and induction of autophagy and apoptosis. One of the most well-recognized mechanisms of apigenin is the capability to promote cell cycle arrest and induction of apoptosis through the p53-related pathway. A further role of apigenin in chemoprevention is the induction of autophagy in several human cancer cell lines. In this review, we discuss the details of apigenin, apoptosis, autophagy, and the role of apigenin in cancer chemoprevention via the induction of apoptosis and autophagy.

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          Most cited references71

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          p62 at the crossroads of autophagy, apoptosis, and cancer.

          The signaling adaptor p62 is a multidomain protein implicated in the activation of the transcription factor NF-kappaB. Recent findings link p62 activity to the extrinsic apoptosis pathway, and Mathew et al. (2009) now show that the modulation of p62 by autophagy is a key factor in tumorigenesis. These findings place p62 at critical decision points that control cell death and survival.
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            Functions of lysosomes.

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              The signaling adaptor p62 is an important NF-kappaB mediator in tumorigenesis.

              The balance between cell death and survival, two critical aspects of oncogenic transformation, determines the outcome of tumorigenesis. Nuclear factor-kappaB (NF-kappaB) is a critical regulator of survival; it is induced by the oncogene Ras and, when inhibited, accounts for the cell death response of Ras-transformed cells. Here, we show that the signaling adaptor p62 is induced by Ras, its levels are increased in human tumors, and it is required for Ras-induced survival and transformation. p62-/- mice are resistant to Ras-induced lung adenocarcinomas. p62 is necessary for Ras to trigger IkappaB kinase (IKK) through the polyubiquitination of tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6), and its deficiency produces increased reactive oxygen species (ROS) levels, which account for the enhanced cell death and reduced tumorigenicity of Ras in the absence of p62.
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                Author and article information

                Journal
                J Cancer Prev
                J Cancer Prev
                JCP
                Journal of Cancer Prevention
                Korean Society of Cancer Prevention
                2288-3649
                2288-3657
                December 2016
                30 December 2016
                : 21
                : 4
                : 216-226
                Affiliations
                Department of Pharmacy, College of Pharmacy, Molecular Inflammation Research Center for Aging Intervention, Pusan National University, Busan, Korea
                Author notes
                Correspondence to: Nam Deuk Kim Department of Pharmacy, College of Pharmacy, Pusan National University, 2 Busandaehak-ro 63beon-gil, Geumjeong-gu, Busan 46241, Korea, Tel: +82-51-510-2801, Fax: +82-51-513-6754, E-mail: nadkim@ 123456pusan.ac.kr , ORCID: Nam Deuk Kim, http://orcid.org/0000-0001-9033-9865
                Article
                jcp-21-216
                10.15430/JCP.2016.21.4.216
                5207605
                28053955
                cc02b647-8cfe-43bf-bdad-2be0ec9ffe8d
                Copyright © 2016 Korean Society of Cancer Prevention

                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
                : 16 November 2016
                : 28 November 2016
                : 29 November 2016
                Categories
                Review

                apigenin,chemoprevention,apoptosis,autophagy
                apigenin, chemoprevention, apoptosis, autophagy

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