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      In Vitro Anticancer and Proapoptotic Activities of Steroidal Glycosides from the Starfish Anthenea aspera

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          Abstract

          New marine glycoconjugates—the steroidal glycosides designated as anthenosides V–X ( 13)—and the seven previously known anthenosides E ( 4), G ( 5), J ( 6), K ( 7), S1 ( 8), S4 ( 9), and S6 ( 10) were isolated from the extract of the tropical starfish Anthenea aspera. The structures of 13 were elucidated by extensive NMR and ESIMS techniques. Glycoside 1 contains a rare 5α-cholest-8(14)-ene-3α,7β,16α-hydroxysteroidal nucleus. Compounds 2 and 3 were isolated as inseparable mixtures of epimers. All investigated compounds ( 110) at nontoxic concentrations inhibited colony formation of human melanoma RPMI-7951, breast cancer T-47D, and colorectal carcinoma HT-29 cells to a variable degree. The mixture of 6 and 7 possessed significant anticancer activity and induced apoptosis of HT-29 cells. The molecular mechanism of the proapoptotic action of this mixture was shown to be associated with the regulation of anti- and proapoptotic protein expression followed by the activation of initiator and effector caspases.

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          Most cited references 28

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          Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-years for 32 Cancer Groups, 1990 to 2015: A Systematic Analysis for the Global Burden of Disease Study

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            The soft agar colony formation assay.

            Anchorage-independent growth is the ability of transformed cells to grow independently of a solid surface, and is a hallmark of carcinogenesis. The soft agar colony formation assay is a well-established method for characterizing this capability in vitro and is considered to be one of the most stringent tests for malignant transformation in cells. This assay also allows for semi-quantitative evaluation of this capability in response to various treatment conditions. Here, we will demonstrate the soft agar colony formation assay using a murine lung carcinoma cell line, CMT167, to demonstrate the tumor suppressive effects of two members of the Wnt signaling pathway, Wnt7A and Frizzled-9 (Fzd-9). Concurrent overexpression of Wnt7a and Fzd-9 caused an inhibition of colony formation in CMT167 cells. This shows that expression of Wnt7a ligand and its Frizzled-9 receptor is sufficient to suppress tumor growth in a murine lung carcinoma model.
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              Molecular biology of Bax and Bak activation and action.

              Bax and Bak are two nuclear-encoded proteins present in higher eukaryotes that are able to pierce the mitochondrial outer membrane to mediate cell death by apoptosis. Thus, organelles recruited by nucleated cells to supply energy can be recruited by Bax and Bak to kill cells. The two proteins lie in wait in healthy cells where they adopt a globular α-helical structure, seemingly as monomers. Following a variety of stress signals, they convert into pore-forming proteins by changing conformation and assembling into oligomeric complexes in the mitochondrial outer membrane. Proteins from the mitochondrial intermembrane space then empty into the cytosol to activate proteases that dismantle the cell. The arrangement of Bax and Bak in membrane-bound complexes, and how the complexes porate the membrane, is far from being understood. However, recent data indicate that they first form symmetric BH3:groove dimers which can be linked via an interface between the α6-helices to form high order oligomers. Here, we review how Bax and Bak change conformation and oligomerize, as well as how oligomers might form a pore. This article is part of a Special Issue entitled Mitochondria: the deadly organelle. Crown Copyright © 2010. Published by Elsevier B.V. All rights reserved.
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                Author and article information

                Journal
                Mar Drugs
                Mar Drugs
                marinedrugs
                Marine Drugs
                MDPI
                1660-3397
                01 November 2018
                November 2018
                : 16
                : 11
                Affiliations
                [1 ]G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch of the Russian Academy of Sciences, Pr. 100-let Vladivostoku 159, 690022 Vladivostok, Russia; malyarenko.os@ 123456gmail.com (O.S.M.); kicha@ 123456piboc.dvo.ru (A.A.K.); ivanchina@ 123456piboc.dvo.ru (N.V.I.); kaaniv@ 123456piboc.dvo.ru (A.I.K.); paveldmt@ 123456piboc.dvo.ru (P.S.D.); swetlana_e@ 123456mail.ru (S.P.E.); stonik@ 123456piboc.dvo.ru (V.A.S.)
                [2 ]Far Eastern Federal University, Sukhanova Str. 8, 690000 Vladivostok, Russia
                Author notes
                [* ]Correspondence: malyarenko-tv@ 123456mail.ru ; Tel.: +7-423-2312-360; Fax: +7-423-2314-050
                Article
                marinedrugs-16-00420
                10.3390/md16110420
                6266882
                30388749
                © 2018 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/).

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