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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

A lectin from Bothrops leucurus snake venom raises cytosolic calcium levels and promotes B16-F10 melanoma necrotic cell death via mitochondrial permeability transition

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Author(s):
Aranda-Souza, Mary A. [1, 2] ; Rossato, Franco A. [1] ; Costa, Rute A. P. [1] ; Figueira, Tiago R. [1] ; Castilho, Roger F. [1] ; Guarniere, Miriam C. [3] ; Nunes, Erika S. [2] ; Coelho, Luana C. B. B. [2] ; Correia, Maria T. S. [2] ; Vercesi, Anibal E. [1]
Total Authors: 10
Affiliation:
[1] Univ Estadual Campinas, Fac Med Sci, Dept Clin Pathol, BR-13083887 Campinas, SP - Brazil
[2] Univ Fed Pernambuco, Ctr Biol Sci, Dept Biochem, Recife, PE - Brazil
[3] Univ Fed Pernambuco, Ctr Biol Sci, Dept Zool, Recife, PE - Brazil
Total Affiliations: 3
Document type: Journal article
Source: Toxicon; v. 82, p. 97-103, MAY 2014.
Web of Science Citations: 20
Abstract

BIL, a galactose-binding C-type lectin purified from Bothrops leucurus snake venom, exhibits anticancer activity. The current study was designed to elucidate the cellular mechanisms by which BR, induces melanoma cell death. The viabilities of B16-F10 melanoma cells and HaCaT keratinocytes treated with BIL were evaluated. Necrotic and apoptotic cell death, cytosolic Ca2+ levels, mitochondrial Ca2+ transport and superoxide levels were assessed in B16-F10 melanoma cells exposed to BIL. We found that treatment with BIL caused dose-dependent necrotic cell death in B16-F10 melanoma cells. Conversely, the viability of non-tumorigenic HaCaT cells was not affected by similar doses of BIL. BIL-induced B16-F10 necrosis was preceded by a significant (2-fold) increase in cytosolic calcium concentrations and a significant (3-fold) increase in mitochondrial superoxide generation. It is likely that BlL treatment triggers B16-F10 cell death via mitochondrial permeability transition (MPT) pore opening because the pharmacological MPT inhibitors bongkrekic acid and Debio 025 greatly attenuated BIL-induced cell death. Experiments evaluating mitochondrial Ca2+ transport in permeabilized B16-F10 cells strongly supported the hypothesis that BIL rapidly stimulates cyclosporine A-sensitive Ca2+-induced MPT pore opening. We therefore conclude that BIL causes selective B16-F10 melanoma cell death via dysregulation of cellular Ca2+ homeostasis and Ca2+-induced opening of MPT pore. (C) 2014 Elsevier Ltd. All rights reserved. (AU)

FAPESP's process: 11/51800-1 - Muscle damage induced by eccentric exercise: involvement of mitochondria and interactions with statin myotoxicity
Grantee:Tiago Rezende Figueira
Support type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 11/50400-0 - Mitochondrial energy metabolism, redox state and functionality in cell death and cardiometabolic and neurodegenerative disorders
Grantee:Aníbal Eugênio Vercesi
Support type: Research Projects - Thematic Grants
FAPESP's process: 12/07424-8 - Mitochondrial bioenergetics in TNF-alpha receptor 1 knockout mice: effect on fat diet-induced obesity
Grantee:Mary Angela Aranda de Souza
Support type: Scholarships in Brazil - Doctorate