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      Antitumor Compounds from Marine Actinomycetes

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          Abstract

          Chemotherapy is one of the main treatments used to combat cancer. A great number of antitumor compounds are natural products or their derivatives, mainly produced by microorganisms. In particular, actinomycetes are the producers of a large number of natural products with different biological activities, including antitumor properties. These antitumor compounds belong to several structural classes such as anthracyclines, enediynes, indolocarbazoles, isoprenoides, macrolides, non-ribosomal peptides and others, and they exert antitumor activity by inducing apoptosis through DNA cleavage mediated by topoisomerase I or II inhibition, mitochondria permeabilization, inhibition of key enzymes involved in signal transduction like proteases, or cellular metabolism and in some cases by inhibiting tumor-induced angiogenesis. Marine organisms have attracted special attention in the last years for their ability to produce interesting pharmacological lead compounds.

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          Most cited references149

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          Assembly-line enzymology for polyketide and nonribosomal Peptide antibiotics: logic, machinery, and mechanisms.

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            Genomics of Actinobacteria: tracing the evolutionary history of an ancient phylum.

            Actinobacteria constitute one of the largest phyla among bacteria and represent gram-positive bacteria with a high G+C content in their DNA. This bacterial group includes microorganisms exhibiting a wide spectrum of morphologies, from coccoid to fragmenting hyphal forms, as well as possessing highly variable physiological and metabolic properties. Furthermore, Actinobacteria members have adopted different lifestyles, and can be pathogens (e.g., Corynebacterium, Mycobacterium, Nocardia, Tropheryma, and Propionibacterium), soil inhabitants (Streptomyces), plant commensals (Leifsonia), or gastrointestinal commensals (Bifidobacterium). The divergence of Actinobacteria from other bacteria is ancient, making it impossible to identify the phylogenetically closest bacterial group to Actinobacteria. Genome sequence analysis has revolutionized every aspect of bacterial biology by enhancing the understanding of the genetics, physiology, and evolutionary development of bacteria. Various actinobacterial genomes have been sequenced, revealing a wide genomic heterogeneity probably as a reflection of their biodiversity. This review provides an account of the recent explosion of actinobacterial genomics data and an attempt to place this in a biological and evolutionary context.
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              Polyamines and cancer: old molecules, new understanding.

              The amino-acid-derived polyamines have long been associated with cell growth and cancer, and specific oncogenes and tumour-suppressor genes regulate polyamine metabolism. Inhibition of polyamine synthesis has proven to be generally ineffective as an anticancer strategy in clinical trials, but it is a potent cancer chemoprevention strategy in preclinical studies. Clinical trials, with well-defined goals, are now underway to evaluate the chemopreventive efficacy of inhibitors of polyamine synthesis in a range of tissues.
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                Author and article information

                Journal
                Mar Drugs
                MD
                Marine Drugs
                Molecular Diversity Preservation International
                1660-3397
                June 2009
                11 June 2009
                : 7
                : 2
                : 210-248
                Affiliations
                Departamento de Biología Funcional e Instituto Universitario de Oncología del Principado de Asturias (I.U.O.P.A), Universidad de Oviedo, 33006 Oviedo, Spain; E-Mails: olanocarlos@ 123456uniovi.es (C.O.); cmendezf@ 123456uniovi.es (C.M.)
                Author notes
                *Author to whom correspondence should be addressed; E-Mail: jasalas@ 123456uniovi.es ; Tel.: +34-985-103652; Fax: +34-985-103652
                Article
                md-07-00210
                10.3390/md7020210
                2707044
                19597582
                40af3ae2-7916-4be3-919e-418a815558f0
                © 2009 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland.

                This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                : 25 May 2009
                : 8 June 2009
                : 11 June 2009
                Categories
                Review

                Pharmacology & Pharmaceutical medicine
                indolocarbazole,non-ribosomal peptide synthetase,macrolide,polyketide synthase,anthracycline

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