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      Progress in Research on the Role of Flavonoids in Lung Cancer

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          Abstract

          Lung cancer is the leading cause of cancer deaths worldwide. Therefore, for the prevention, diagnosis, prognosis and treatment of lung cancer, efficient preventive strategies and new therapeutic strategies are needed to face these challenges. Natural bioactive compounds and particular flavonoids compounds have been proven to have an important role in lung cancer prevention and of particular interest is the dose used for these studies, to underline the molecular effects and mechanisms at a physiological concentration. The purpose of this review was to summarize the current state of knowledge regarding relevant molecular mechanisms involved in the pharmacological effects, with a special focus on the anti-cancer role, by regulating the coding and non-coding genes. Furthermore, this review focused on the most commonly altered and most clinically relevant oncogenes and tumor suppressor genes and microRNAs in lung cancer. Particular attention was given to the biological effect in tandem with conventional therapy, emphasizing the role in the regulation of drug resistance related mechanisms.

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          Most cited references85

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          Flavonoids in Cancer and Apoptosis

          Cancer is the second leading cause of death globally. Although, there are many different approaches to cancer treatment, they are often painful due to adverse side effects and are sometimes ineffective due to increasing resistance to classical anti-cancer drugs or radiation therapy. Targeting delayed/inhibited apoptosis is a major approach in cancer treatment and a highly active area of research. Plant derived natural compounds are of major interest due to their high bioavailability, safety, minimal side effects and, most importantly, cost effectiveness. Flavonoids have gained importance as anti-cancer agents and have shown great potential as cytotoxic anti-cancer agents promoting apoptosis in cancer cells. In this review, a summary of flavonoids and their effectiveness in cancer treatment targeting apoptosis has been discussed.
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            Flavonoids as prospective compounds for anti-cancer therapy.

            Flavonoids, which are polyphenolic compounds, are a class of plant secondary metabolites possessing a broad spectrum of pharmacological activity including anti-cancer activities. They have been reported to interfere in the initiation, promotion and progression of cancer by modulating different enzymes and receptors in signal transduction pathways related to cellular proliferation, differentiation, apoptosis, inflammation, angiogenesis, metastasis and reversal of multidrug resistance. Due to their multiple molecular mechanisms of action, flavonoids (both natural and synthetic analogs) are being investigated for their potential applications in anti-cancer therapies. In this review article, the main molecular mechanisms of action of flavonoids attributing to their potential anti-cancer activities have been discussed and the key structural features required for their activity are highlighted. Copyright © 2013 Elsevier Ltd. All rights reserved.
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              Ubiquitylation in apoptosis: a post-translational modification at the edge of life and death.

              The proper regulation of apoptosis is essential for the survival of multicellular organisms. Furthermore, excessive apoptosis can contribute to neurodegenerative diseases, anaemia and graft rejection, and diminished apoptosis can lead to autoimmune diseases and cancer. It has become clear that the post-translational modification of apoptotic proteins by ubiquitylation regulates key components in cell death signalling cascades. For example, ubiquitin E3 ligases, such as MDM2 (which ubiquitylates p53) and inhibitor of apoptosis (IAP) proteins, and deubiquitinases, such as A20 and ubiquitin-specific protease 9X (USP9X) (which regulate the ubiquitylation and degradation of receptor-interacting protein 1 (RIP1) and myeloid leukaemia cell differentiation 1 (MCL1), respectively), have important roles in apoptosis. Therapeutic agents that target apoptotic regulatory proteins, including those that are part of the ubiquitin-proteasome system, might afford clinical benefits.
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                02 September 2019
                September 2019
                : 20
                : 17
                : 4291
                Affiliations
                [1 ]Research Center for Functional Genomics and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 23 Marinescu Street, 40015 Cluj-Napoca, Romania
                [2 ]Biozoon GmbH, D-27572 Bremerhaven, Germany
                [3 ]Department of Pathology, “Prof. Dr. Ion Chiricuta” Oncology Institute, 400015 Cluj-Napoca, Romania
                [4 ]Department of Pathology Iuliu Hatieganu, University of Medicine and Pharmacy, 400015 Cluj-Napoca, Romania
                [5 ]MEDFUTURE-Research Center for Advanced Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania, 23 Marinescu Street, 40015 Cluj-Napoca, Romania
                [6 ]Department of Functional Genomics and Experimental Pathology, The Oncology Institute “Prof. Dr. Ion Chiricuta”, Republicii 34th street, 400015 Cluj-Napoca, Romania
                Author notes
                Author information
                https://orcid.org/0000-0001-9574-0914
                https://orcid.org/0000-0002-3055-4747
                https://orcid.org/0000-0003-3856-3784
                Article
                ijms-20-04291
                10.3390/ijms20174291
                6747533
                31480720
                90efe503-1f9b-4bcb-ba74-762d28263f53
                © 2019 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
                : 21 August 2019
                : 30 August 2019
                Categories
                Review

                Molecular biology
                flavonoids,lung cancer,cellular signaling pathways
                Molecular biology
                flavonoids, lung cancer, cellular signaling pathways

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