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Amblyomin-X induces ER stress, mitochondrial dysfunction, and caspase activation in human melanoma and pancreatic tumor cell.
Morais, Katia L P; Pacheco, Mario Thiego Fernandes; Berra, Carolina Maria; Bosch, Rosemary V; Sciani, Juliana Mozer; Chammas, Roger; de Freitas Saito, Renata; Iqbal, Asif; Chudzinski-Tavassi, Ana Marisa.
Afiliação
  • Morais KL; Biochemistry and Biophysics Laboratory, Butantan Institute, Av. Vital Brazil, 1500, São Paulo, SP, 05503-900, Brazil.
  • Pacheco MT; Department of Biochemistry, Federal University of São Paulo, São Paulo, SP, Brazil.
  • Berra CM; Biochemistry and Biophysics Laboratory, Butantan Institute, Av. Vital Brazil, 1500, São Paulo, SP, 05503-900, Brazil.
  • Bosch RV; Biochemistry Department, Institute of Chemistry, University of São Paulo, São Paulo, Brazil.
  • Sciani JM; Biochemistry and Biophysics Laboratory, Butantan Institute, Av. Vital Brazil, 1500, São Paulo, SP, 05503-900, Brazil.
  • Chammas R; Biochemistry and Biophysics Laboratory, Butantan Institute, Av. Vital Brazil, 1500, São Paulo, SP, 05503-900, Brazil.
  • de Freitas Saito R; Experimental Oncology Medical Investigation Laboratory - LIM/24, University of São Paulo School of Medicine, São Paulo, SP, Brazil.
  • Iqbal A; Experimental Oncology Medical Investigation Laboratory - LIM/24, University of São Paulo School of Medicine, São Paulo, SP, Brazil.
  • Chudzinski-Tavassi AM; Biochemistry and Biophysics Laboratory, Butantan Institute, Av. Vital Brazil, 1500, São Paulo, SP, 05503-900, Brazil.
Mol Cell Biochem ; 415(1-2): 119-31, 2016 Apr.
Article em En | MEDLINE | ID: mdl-27015684
During the last two decades, new insights into proteasome function and its role in several human diseases made it a potential therapeutic target. In this context, Amblyomin-X is a Kunitz-type FXa inhibitor similar to endogenous tissue factor pathway inhibitor (TFPI) and is a novel proteasome inhibitor. Herein, we have demonstrated Amblyomin-X cytotoxicity to different tumor cells lines such as pancreatic (Panc1, AsPC1BxPC3) and melanoma (SK-MEL-5 and SK-MEL-28). Of note, Amblyomin-X was not cytotoxic to normal human fibroblast cells. In addition, Amblyomin-X promoted accumulation of ER stress markers (GRP78 and GADD153) in sensitive (SK-MEL-28) and bortezomib-resistant (Mia-PaCa-2) tumor cells. The intracellular calcium concentration [Ca(2+)] i was slightly modulated in human tumor cells (SK-MEL-28 and Mia-PaCa-2) after 24 h of Amblyomin-X treatment. Furthermore, Amblyomin-X induced mitochondrial dysfunction, cytochrome-c release, PARP cleavage, and activation of caspase cascade in both human tumor (SK-MEL-28 and Mia-PaCa-2) cells. These investigations might help in further understanding of the antitumor properties of Amblyomin-X.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Pancreáticas / Proteínas e Peptídeos Salivares / Caspases / Estresse do Retículo Endoplasmático / Melanoma / Mitocôndrias Limite: Humans Idioma: En Revista: Mol Cell Biochem Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Brasil País de publicação: Holanda

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Pancreáticas / Proteínas e Peptídeos Salivares / Caspases / Estresse do Retículo Endoplasmático / Melanoma / Mitocôndrias Limite: Humans Idioma: En Revista: Mol Cell Biochem Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Brasil País de publicação: Holanda