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Apis mellifera venom induces different cell death pathways in Trypanosoma cruzi

Published online by Cambridge University Press:  19 July 2012

CAMILA M. ADADE ,
GABRIELA S. F. CHAGAS  and
THAÏS SOUTO-PADRÓN
CAMILA M. ADADE
Affiliation:
Laboratório de Biologia Celular e Ultraestrutura, Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de Góes, Centro de Ciências da Saúde, bloco I and Instituto Nacional de Ciência e Tecnologia em Biologia Estrutural e Bioimagens, Universidade Federal do Rio de Janeiro, Ilha do Fundão, Rio de Janeiro, RJ 21941-590, Brazil
GABRIELA S. F. CHAGAS
Affiliation:
Laboratório de Biologia Celular e Ultraestrutura, Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de Góes, Centro de Ciências da Saúde, bloco I and Instituto Nacional de Ciência e Tecnologia em Biologia Estrutural e Bioimagens, Universidade Federal do Rio de Janeiro, Ilha do Fundão, Rio de Janeiro, RJ 21941-590, Brazil
THAÏS SOUTO-PADRÓN*
Affiliation:
Laboratório de Biologia Celular e Ultraestrutura, Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de Góes, Centro de Ciências da Saúde, bloco I and Instituto Nacional de Ciência e Tecnologia em Biologia Estrutural e Bioimagens, Universidade Federal do Rio de Janeiro, Ilha do Fundão, Rio de Janeiro, RJ 21941-590, Brazil
*
*Corresponding author: Tel: +55 (21) 2562 6738. Fax: +55 (21) 2560 8344. E-mail: [email protected]
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Summary

Chagas disease chemotherapy is based on drugs that exhibit toxic effects and have limited efficacy, such as Benznidazole. Therefore, research into new chemotherapeutic agents from natural sources needs to be exploited. Apis mellifera venom consists of many biologically active molecules and has been reported to exhibit remarkable anti-cancer effects, often promoting an apoptosis-like death phenotype. This study demonstrates that A. mellifera venom can affect the growth, viability and ultrastructure of all Trypanosoma cruzi developmental forms, including intracellular amastigotes, at concentrations 15- to 100-fold lower than those required to cause toxic effects in mammalian cells. The ultrastructural changes induced by the venom in the different developmental forms led us to hypothesize the occurrence of different programmed cell death pathways. Autophagic cell death, characterized by the presence of autophagosomes-like organelles and a strong monodansyl cadaverine labelling, appears to be the main death mechanism in epimastigotes. In contrast, increased TUNEL staining, abnormal nuclear chromatin condensation and kDNA disorganization was observed in venom-treated trypomastigotes, suggesting cell death by an apoptotic mechanism. On the other hand, intracellular amastigotes presented a heterogeneous cell death phenotype profile, where apoptosis-like death seemed to be predominant. Our findings confirm the great potential of A. mellifera venom as a source for the development of new drugs for the treatment of neglected diseases such as Chagas disease.

Keywords

Apis melliferaTrypanosoma cruziChagas disease chemotherapyprogrammed cell deathautophagyapoptosis
Type
Research Article
Information
Parasitology , Volume 139 , Issue 11 , September 2012 , pp. 1444 - 1461
Copyright
Copyright © Cambridge University Press 2012

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