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

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]

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

• 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: 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 Opportunities: Scholarships in Brazil - Doctorate
• 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 Opportunities: Scholarships in Brazil - Post-Doctoral
• 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 Opportunities: Research Projects - Thematic Grants