IdentificaÃ§Ã£o do efeito antitumoral de um polipeptÃdeo isolado da ...

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XXXVI Reunião Anual da SBBq e 10th IUBMB Conference, 2007, Salvador. Livro deResumos da XXXVI Reunião Anual da SBBq, 2007.Effect of SCORPAENA PLUMIERI venom and fractions on murine glioblastomacells.Soprani J. 1 , Soares M. A. 1 , Cassoli J. S. 2 Figueiredo S.G. 3 , Santos R.G. 11 Lab. Radiobiologia, Centro de Desenvolvimento da Tecnologia Nuclear,CDTN/CNEN, Minas Gerais, Brazil. 2 Lab. Venenos e Toxinas Animais, ICB, UFMG,Minas Gerais, Brazil. 3 Depto de Ciências Fisiológicas, UFES, Espírito Santo, Brazil.Animal venoms are source of structural templates for development of new therapeuticagents against cancer. The aim of this work was to identify and characterize theantitumoral effect of Scorpaena plumieri venom (SP) and fractions on cultured murineglioblastoma cells. Glioma cells were sensitive to SP in a dose-dependent way.Significant reduction in metabolism followed by morphological disturbs (rounded cellshape and reduction of the cytoplasmic volume) could be observed after treatment bySP. These cytotoxic effects were time and dose-dependent (IC 50 = 3,48µg/mL).Inhibition of cell adhesion and proliferation could also be observed at concentrationshigher than 10µg/mL. Tests of metabolic viability with the fractions have shown thatthe FI, FII, FIV and FVI fractions were equally powerful, reducing the metabolism in70% at concentration of 10µg/mL. Theses fractions proved to have important kallikreinlike,edematogenic, hyaluronidase and caseinolytic activity, respectively. These resultsare an evidence of the worthy anticancer activity of SP and fractions, and morphologicaldisturbs of cells treated with SP are suggestive of the apoptosis occurrence. Furtherstudies are in development in order to characterize the antitumoral mechanisms ofaction of the SP venom and its components.KEY WORDS: scorpionfish, venom, glioblastoma, cytotoxicityFINANCIAL SUPPORT: CNPq, CDTN/CNEN176
IX CONGRESSO BRASILEIRO DE TOXINOLOGIA, 2006, FORTALEZA.JOURNAL VENOMOUS ANIMALS AND TOXINS INCLUDING TROPICALDISEASES, 2006. V. 13. P. 268-268.TITLE: Effect of scorpionfish (SCORPAENA PLUMIERI) venom on culturedmurine glioblastomas cells (RT2) .AUTHORS: SOPRANI J. (1) SILVA P.R.O.(1) SOARES M. A.(1) FIGUEIREDOS.G.(2) SANTOS R.G. (1)AFFILIATIONS: (1) Lab. Radiobiologia, Centro de Desenvolvimento da TecnologiaNuclear – CDTN/CNEN, Minas Gerais, Brasil (2) Depto de Ciências Fisiológicas,Universidade Federal do Espírito Santo, Espírito Santo, Brasil.ABSTRACT: Animal venoms have been recognized as potential sources ofpharmacological agents and physiological tools. The scorpionfishes (Scorpaena) are themost venomous fishes in the Atlantic Ocean. There is very little information on thevenom of scorpionfishes whereas studies describing biological properties of fishvenoms have focused mainly on lionfishes. These venoms often contain activecomponents such as catecholamines, acetylcholine and some enzymatic activities suchas proteolytic hyaluronidases and phosphatases. The effect of Scorpaena plumierivenom (SP) on tumoral cells has not been studied yet. The aim of this work was toidentify and characterize the antitumoral effect of SP on cultured murine glioblastomascells (RT2). RT2 cells were treated with varying concentrations of SP and cytotoxicitywas established using MTT assay. RT2 cells were sensitive to SP in a dose-dependentway. Low concentrations of SP venom did not modified significantly the metabolism ofRT2 cells, but significant reduction in metabolism could be observed at SPconcentrations higher than 5µg/mL (IC 50 =16,7µg/mL) followed by morphologicaldisturbs, such as rounded cell shape and reduction of the cytoplasmic volume. SPeffects on cell adhesion and clonogenicity were also evaluated. Inhibition of celladhesion and proliferation could be observed at concentrations higher than 10µg/mL. Atconcentration of 100µg/mL the cells were completely lysed. Metalloproteases areinvolved in cell-matrix interactions. Since proteolytic activity has been found in manyfish venoms, we evaluated the SP venom proteolytic activity on gelatin by zymography,in order to shed some light on the mechanisms of its effects. We found that SP venompresents gelatinolytic activity that could stand, at least partially, for the anti-tumoraleffect of SP.KEY WORDS: scorpionfish, venom, glioblastoma, metabolismFINANCIAL SUPPORT: CNPq, CDTN/CNENCORRESPONDENCE TO:RG Santos, Lab de Radiobiologia; CDTN/CNEN; C. P. 941; 30123-970; BH- MG –Brasil, santosr@cdtn.br177
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“IDENTIFICAÇÃO DO EFEITO ANTITU
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III
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Agradeço a (os)...Deus, pela vida,
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IDENTIFICATION OF ANTITUMORAL EFFEC
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FIG.29: Zimograma das frações obt
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FIG.54: Fotomicrografia do rim, fí
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LISTA DE ABREVIATURAS• %DI: porce
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3. OBJETIVOS.......................
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5.4.1. Cromatografia de filtração
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241. INTRODUÇÃO
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Segundo estudos realizados pela IAR
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FIG.1: Alterações fisiológicas e
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al., 1997). Os tumores promovem a v
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previne o desencadeamento de um pro
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FIG.2: Imagens ilustrativas dos pro
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citocromo-c (Green & Kroemer, 2004)
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FIG.4: Desenho esquemático da Via
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um ou mais processos envolvidos na
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1.3.3. RadioterapiaA radioterapia p
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sem que se elevem os danos aos teci
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sua disponibilidade comercial, dosi
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Esse mecanismo de acumulação e de
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peçonha de Naja sp. em células de
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pedra (Synanceia verrucosa), arraia
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FIG.6: O peixe escorpião Scorpaena
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Estruturalmente, duas classes de me
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582. JUSTIFICATIVA
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603. OBJETIVOS
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4. MATERIAIS E MÉTODOS4.1. Reagent
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e testadas quanto à atividade gela
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celular através deste teste consis
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Para realização dos experimentos
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Para síntese de sondas radioativas
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proteínas radiomarcadas migram atr
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o 125 I: 80%). Após o cálculo da
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O comportamento e interação das s
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4.17. Experimentos de biodistribui
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4.19. Cálculos farmacocinéticosA
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865. RESULTADOS
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tumorais5.1.1. Avaliação do efeit
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100Sobrevivência (%controle)806040
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FIG.16: Fotomicrografia óptica de
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complementação dos dados obtidos
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FIG.19: Alterações do DNA cromoss
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5.2. Síntese, avaliação da prese
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Os animais receberam injeções com
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plumieri5.4. Purificação da enzim
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5.4.2. Cromatografia de troca aniô
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FIG.30: Perfil cromatográfico obti
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publicados por Carrijo et al. (2005
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*FIG.37: Fotomicrografia óptica de
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FIG.39: Fotomicrografia óptica de
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FIG.40: Análise do DNA cromossomal
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FIG.42: Análise do DNA cromossomal
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FIG.43: Controle de qualidade da [1
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acima expostos confirmam a boa qual
Page 126 and 127: 4%DI/g32* ** *101 10 30 60 180 360
Page 128 and 129: as concentrações desta molécula
Page 130 and 131: Os resultados demonstraram que a co
Page 132 and 133: não gerou anemia, hemólise ou eri
Page 134 and 135: metamielócitos, neutrófilos basto
Page 136 and 137: FIG.54: Fotomicrografia do rim, fí
Page 138 and 139: 6. DISCUSSÃOO câncer é a segunda
Page 140 and 141: Os experimentos de citotoxicidade m
Page 142 and 143: necessidade da presença do gene P5
Page 144 and 145: estratégias terapêuticas contra t
Page 146 and 147: distribuição e captação do fár
Page 148 and 149: 7.1. CONCLUSÕES• A peçonha do p
Page 150 and 151: 8. REFERÊNCIAS BIBLIOGRÁFICASABU-
Page 152 and 153: Phase III randomized trial of amifo
Page 154 and 155: Camundongos Fêmeas Castradas e Nã
Page 156 and 157: HADDAD, V. JR. Atlas de animais aqu
Page 158 and 159: KOMAROVA, E. A.; CHERNOV, M. V.; FR
Page 160 and 161: NOLLET, F.; KOOLS, P.; VAN ROY, F.
Page 162 and 163: REDDY, L.; ODHAV, B.; BHOOLA, K.D.
Page 164 and 165: TARAPHDAR, A.K.; ROY, M.; BHATTACHA
Page 166 and 167: 166APÊNDICE
Page 168 and 169: FIG.56: Emissão de partículas e r
Page 170 and 171: Quando um feixe de radiação ioniz
Page 172 and 173: APENDICE BAvaliação preliminar do
Page 174 and 175: 174ANEXOS
Page 178 and 179: 9TH PAN AMERICAM SECTION CONGRESS I
Page 180 and 181: The genus Scorpaena, which includes
Page 182 and 183: preparation radiochemical purity. T
Page 184 and 185: In spite of slight, lung (2.3%ID/g)
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