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J Drug Target ; 16(5): 379-88, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18569282

RESUMO

OBJECTIVE: To detect the effect and cytotoxicity of luteinizing hormone-releasing hormone-Pseudomonas aeruginosa exotoxin 40 (LHRH-PE40) on target cells using LHRH receptors (LHRHR). METHODS: The affinity of LHRH-PE40 and LHRH binding to LHRHR on the membrane surface of target cells were measured by enzyme linked immunosorbent assay. Morphological observations with light microscope were used to analyze its receptor pathway, with Spiegelmer, and cytotoxicity. IC(50) values of LHRH-PE40, which caused 50% inhibition of tumor cell growth were evaluated by MTT assay. The target cells were exposed to LHRH-PE40 and its cytotoxicity was analyzed by scanning and transmission electron microscopies, agarose gel electrophoresis, and flow cytometry. RESULTS: LHRH-PE40 killed target cells by LHRHR pathway. The morphological changes in these cells showed decreased cell size, cytoplasmic membrane blebbing, and chromatin condensation and margination. At a certain concentration and time point, HeLa cells were also induced to undergo programmed cell death. CONCLUSION: LHRH-PE40 induced target cells apoptosis via LHRHR.


Assuntos
ADP Ribose Transferases/genética , Antineoplásicos/farmacologia , Toxinas Bacterianas/genética , Exotoxinas/genética , Hormônio Liberador de Gonadotropina/genética , Receptores LHRH/fisiologia , Proteínas Recombinantes de Fusão/farmacologia , Fatores de Virulência/genética , Apoptose/efeitos dos fármacos , Ligação Competitiva , Divisão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Eletroforese em Gel de Ágar , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Humanos , Microscopia Eletrônica , Proteínas Recombinantes de Fusão/genética , Exotoxina A de Pseudomonas aeruginosa
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