Tumor cytotoxicity of leucurolysin-B, a P-III snake venom metalloproteinase from Bothrops leucurus

Gabriel LM (1), Sanchez EF (2), Silva SG (2), Santos RG (1, 3)

(1) Center for Development of Nuclear Technology/Brazilian Nuclear Energy Commission (CDTN/ CNEN), Belo Horizonte, Minas Gerais State, Brazil; (2) Ezequiel Dias Foundation (FUNED), Belo Horizonte, Minas Gerais State, Brazil; (3) Brazil National Institute of Science and Technology of Molecular Medicine (INCT-MM), Belo Horizonte, Minas Gerais State, Brazil.

Abstract: Although it has been demonstrated that venoms and toxins from some snakes are able to influence the growth of tumor cells, few antitumoral compounds from Bothrops leucurus venom have been characterized. Leucurolysin-B (leuc-B) is a metalloproteinase class P-III isolated from B. leucurus which possesses an ECD-disintegrin domain. Both ECD-disentegrin and RGD-disintegrin are able to bind to cell surface integrins and inhibit their adherence to their natural ligands. In the present study, the potential efficacy and the cytotoxic effects of leuc-B on glioblastoma, breast cancer and melanoma cell lines were analyzed. The effect of leuc-B on cancer cell survival was evaluated and its 50% inhibitory concentration (IC50) was determined. Morphological alterations were monitored by contrast phase and fluorescent microscopy. The results demonstrated that leuc-B has potent cytotoxic effect in a micromolar range against all evaluated cancer cell lines. Morphologically, dying cells showed fragmentation, condensation of their contents concomitant with shrinkage and appearance of vacuoles. This study reports for the first time the cytotoxic effect of leuc-B from B. leucurus snake venom on tumor cells.

Key words: snake venom, leucurolysin-B, ECD-disintegrin, tumor,in vitro study.

ACKNOWLEDGEMENTS

This work was financially supported by The Nuclear Technology Development Center /National Nuclear Energy Commission (CDTN/CNEN), the Brazilian agencies The State of Minas Gerais Research Foundation (FAPEMIG), Coordination for the Improvement of Higher Education Personnel (CAPES) and the National Institute of Science and Technology of Molecular Medicine (INCT-MM). LMG received a fellowship from CNEN.

COPYRIGHT

© CEVAP 2012

SUBMISSION STATUS

Received: July 6, 2011.

Accepted: September 15, 2011.

Abstract published online: October 6, 2011.

Full paper published online: February 28, 2012.

CONFLICTS OF INTEREST

The authors declare no conflicts of interest.

FINANCIAL SOURCE

The Nuclear Technology Development Center/ National Nuclear Energy Commission (CDTN/CNEN), The National Council for Scientific and Technological Development (CNPq), and The State of Minas Gerais Research Foundation (FAPEMIG) provided the financial grants.

ETHICS COMMITTEE APPROVAL

The present study was approved by the Ethics Committee of the Federal University of Minas Gerais (UFMG), protocol number 152/2007.

CORRESPONDENCE TO

Raquel Gouvêa dos Santos, Av. Antônio Carlos, 6627, Pampulha, Belo Horizonte, MG, 31270-901, Brasil. Phone: +55 31 3069 3177. Fax: +55 31 3069 3356. Email: santosr@cdtn.br.