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      Natural Compounds as Modulators of Cell Cycle Arrest: Application for Anticancer Chemotherapies

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          Abstract

          Natural compounds from various plants, microorganisms and marine species play an important role in the discovery novel components that can be successfully used in numerous biomedical applications, including anticancer therapeutics. Since uncontrolled and rapid cell division is a hallmark of cancer, unraveling the molecular mechanisms underlying mitosis is key to understanding how various natural compounds might function as inhibitors of cell cycle progression. A number of natural compounds that inhibit the cell cycle arrest have proven effective for killing cancer cells in vitro, in vivo and in clinical settings. Significant advances that have been recently made in the understanding of molecular mechanisms underlying the cell cycle regulation using the chemotherapeutic agents is of great importance for improving the efficacy of targeted therapeutics and overcoming resistance to anticancer drugs, especially of natural origin, which inhibit the activities of cyclins and cyclin-dependent kinases, as well as other proteins and enzymes involved in proper regulation of cell cycle leading to controlled cell proliferation.

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          Most cited references298

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          Principles of CDK regulation.

          D Morgan (1995)
          As key regulators of the cell cycle, the cyclin-dependent kinases must be tightly regulated by extra- and intracellular signals. The activity of cyclin-dependent kinases is controlled by four highly conserved biochemical mechanisms, forming a web of regulatory pathways unmatched in its elegance and intricacy.
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            Dynamic instability of microtubule growth.

            We report here that microtubules in vitro coexist in growing and shrinking populations which interconvert rather infrequently. This dynamic instability is a general property of microtubules and may be fundamental in explaining cellular microtubule organization.
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              Cyclin is degraded by the ubiquitin pathway.

              Cyclin degradation is the key step governing exit from mitosis and progress into the next cell cycle. When a region in the N terminus of cyclin is fused to a foreign protein, it produces a hybrid protein susceptible to proteolysis at mitosis. During the course of degradation, both cyclin and the hybrid form conjugates with ubiquitin. The kinetic properties of the conjugates indicate that cyclin is degraded by ubiquitin-dependent proteolysis. Thus anaphase may be triggered by the recognition of cyclin by the ubiquitin-conjugating system.
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                Author and article information

                Journal
                Curr Genomics
                Curr. Genomics
                CG
                Current Genomics
                Bentham Science Publishers
                1389-2029
                1875-5488
                April 2017
                April 2017
                : 18
                : 2
                : 106-131
                Affiliations
                [1 ]Departamento de Ciencias de la Salud;
                [2 ]Departamento de Ciencias Naturales;
                [3 ]Departamento de Química, Universidad Técnica Particular de Loja, Loja, Ecuador
                Author notes
                [* ]Address correspondence to this author at the UTPL, San Cayetano Alto, Calle París, Loja, Ecuador; Tel: 593-07-370-1444; Ext: 3005;, E-mail: nbailon@ 123456utpl.edu.ec
                Article
                CG-18-106
                10.2174/1389202917666160808125645
                5345333
                28367072
                501e17c9-62ee-4e48-b1b2-e6da328a3857
                © 2017 Bentham Science Publishers

                This is an open access article licensed under the terms of the Creative Commons Attribution-Non-Commercial 4.0 International Public License (CC BY-NC 4.0) (https://creativecommons.org/licenses/by-nc/4.0/legalcode), which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

                History
                : 16 October 2015
                : 13 November 2015
                : 20 November 2015
                Categories
                Article

                Genetics
                cancer,natural compounds,mitosis,cell cycle arrest
                Genetics
                cancer, natural compounds, mitosis, cell cycle arrest

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