Mastoparan induces apoptosis in B1 6F10-Nex2 melanoma cells via the intrinsic mitochondrial pathway and displays antitumor activity in vivo

Mastoparan is an a-helical and amphipathic tetradecapeptide obtained from the venom of the wasp Vespula lewisii. This peptide exhibits a wide variety of biological effects, including antimicrobial activity, increased histamine release from mast cells, induction of a potent mitochondrial permeability transition and tumor cell cytotoxicity. Here, the effects of mastoparan in malignant melanoma were studied using the murine model of B16F10-Nex2 cells. in vitro, mastoparan caused melanoma cell death by the mitochondrial apoptosis pathway, as evidenced by the Annexin V-FITC/PI assay, loss of mitochondrial membrane potential (Delta psi(m)), generation of reactive oxygen species, DNA degradation and cell death signaling. Most importantly, mastoparan reduced the growth of subcutaneous melanoma in syngeneic mice and increased their survival. the present results show that mastoparan induced caspase-dependent apoptosis in melanoma cells through the intrinsic mitochondrial pathway protecting the mice against tumor development. (C) 2014 Elsevier Inc. All rights reserved.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)INCT ToxConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Butantan Inst, Biochem & Biophys Lab, São Paulo, SP, BrazilUniversidade Federal de São Paulo, Dept Microbiol Immunol & Parasitol, Expt Oncol Unit UNONEX, São Paulo, SP, BrazilUniv São Paulo, Inst Biomed Sci, Dept Immunol, BR-05508 São Paulo, SP, BrazilUniv São Paulo, Cell & Mol Therapy Ctr NUCEL NETCEM, São Paulo, BrazilUniv São Paulo, Sch Med, Lab Genet & Mol Hematol LIM31, BR-05508 São Paulo, BrazilButantan Inst, Lab Genet, São Paulo, SP, BrazilUniversidade Federal de São Paulo, Dept Microbiol Immunol & Parasitol, Expt Oncol Unit UNONEX, São Paulo, SP, BrazilFAPESP: 2010/51077-5Web of Scienc

Chalcones and N-acylhydrazones: direct analogues? Exploratory data analysis applied to potential novel antileishmanial agents

Leishmaniasis is an important health and social problem for which there is limited effective therapy. Chalcones and N-acylhydrazones have been studied as promising antileishmanial agents in enzymatic inhibition and in vitro assays. Since these chemical classes of compounds also resemble each other structurally, it would be useful to investigate whether they share direct analogy. Exploratory data analysis was applied to a library of chalcones and nitrated N-acylhydrazones assayed against Leishmania donovani to investigate their similarity. Under the conditions applied in the present study, the two classes did not present functional or structural analogy.<br>As leishmanioses são importantes problemas sociais e de saúde pública para os quais a terapia farmacológica atual é, ainda, limitada. Chalconas e N-acilidrazonas têm sido estudadas como promissores agentes leishmanicidas tanto em ensaios in vitro quanto em ensaios de inibição de cisteíno-proteases importantes para o parasito. Uma vez que estas classes de compostos apresentam similaridade bidimensional, seria interessante estudar se estes compostos guardariam relação de analogia direta entre si. Análise exploratória de dados foi aplicada, então, à biblioteca de chalconas e N-acilidrazonas nitradas ensaiadas contra Leishmania donovani para investigar suas relações de similaridade. Os resultados mostraram que, ao menos sob as condições consideradas neste estudo, as duas classes de compostos não apresentam analogia estrutural e funcional simultaneamente, embora elas apresentem alguma similaridade estrutural