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Therapeutic potential evaluation of L-amino acid oxidases isolated from snake venoms as antitumor: genotoxicity and gene expression studies

Grant number: 15/00740-0
Support Opportunities:Scholarships in Brazil - Post-Doctoral
Effective date (Start): May 01, 2015
Effective date (End): December 31, 2018
Field of knowledge:Health Sciences - Pharmacy
Principal Investigator:Suely Vilela
Grantee:Tássia Rafaella Costa
Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated research grant:11/23236-4 - Native and recombinant animal toxins: functional, structural and molecular analysis, AP.TEM


The L-amino acid oxidases isolated and characterized from snake venoms (SV-LAAOs) have become important candidates for models in the development of new drugs and biological tools. Studies have demonstrated that SV-LAAOs isolated from different genera of snakes can promote alterations in the metabolism of cancer cells, and induction of apoptosis by activation of multiple pathways. This pharmacological effect can be explained, in part, by the generation of hydrogen peroxide formed during the catalytic cycle of LAAOs. However, data related to the possible genotoxic and mutagenic effects that these venom proteins can cause to human cells are very scarce. The main objective of this project is the identification of the genomic danger that LAAOs from Calloselasma rhodostoma (CR-LAAO), Bothrops jararaca (BjarLAAO-I) and Crotalus durissus terrificus snake venoms can offer to human cells. For this, we will investigate the ability of these enzymes to cause genotoxic and mutagenic damage in human cells (HepG2 and PBMC), using in vitro assays that quantify the damage caused in the DNA and chromosomes of these cells (comet test and micronucleus). Moreover, we will evaluate whether treatment with different concentrations of the SV-LAAOs is able to induce activation of DNA repair mechanisms, by detecting the expression of genes involved in this process. These data will be very important for the direction of our research in pursuit of the development of more effective antitumor drugs or adjuncts in the treatment of different cancers.

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Scientific publications (8)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
BOLDRINI-FRANCA, JOHARA; PINHEIRO-JUNIOR, ERNESTO LOPES; PEIGNEUR, STEVE; PUCCA, MANUELA BERTO; CERNI, FELIPE AUGUSTO; BORGES, RAFAEL JUNQUEIRA; COSTA, TASSIA RAFAELLA; IMAI CARONE, SANTE EMMANUEL; DE MATTOS FONTES, MARCOS ROBERTO; SAMPAIO, SUELY VILELA; et al. Beyond hemostasis: a snake venom serine protease with potassium channel blocking and potential antitumor activities. SCIENTIFIC REPORTS, v. 10, n. 1, . (15/18432-0, 15/00740-0, 18/14158-9, 16/24191-8, 15/16714-8, 17/13485-3, 11/23236-4, 17/14035-1, 16/04761-4, 14/16182-3, 15/17286-0)
BENATI, ROGERIO BODINI; COSTA, TASSIA RAFAELA; CACEMIRO, MAIRA DA COSTA; SAMPAIO, SUELY VILELA; DE CASTRO, FABIOLA ATTIE; BURIN, SANDRA MARA. Cytotoxic and pro-apoptotic action of MjTX-I, a phospholipase A2 isolated from Bothrops moojeni snake venom, towards leukemic cells. Journal of Venomous Animals and Toxins including Tropical Diseases, v. 24, . (15/00740-0, 15/25637-7, 11/23236-4, 14/04234-9)
AMORIM, FERNANDA GOBBI; COSTA, TASSIA RAFAELA; BAIWIR, DOMINIQUE; DE PAUW, EDWIN; QUINTON, LOIC; SAMPAIO, SUELY VILELA. Proteopeptidomic, Functional and Immunoreactivity Characterization of Bothrops moojeni Snake Venom: Influence of Snake Gender on Venom Composition. TOXINS, v. 10, n. 5, . (15/00740-0, 15/26609-7, 16/20641-9, 11/23236-4)
CARONE, SANTE E. I.; COSTA, TASSIA R.; BURIN, SANDRA M.; CINTRA, ADELIA C. O.; ZOCCAL, KARINA F.; BIANCHINI, FRANCINE J.; TUCCI, LUIZ F. F.; FRANCO, JOAO J.; TORQUETI, MARIA R.; FACCIOLI, LUCIA H.; et al. A new L-amino acid oxidase from Bothrops jararacussu snake venom: Isolation, partial characterization, and assessment of pro-apoptotic and antiprotozoal activities. International Journal of Biological Macromolecules, v. 103, p. 25-35, . (15/00740-0, 11/23236-4, 15/25637-7)
LEAO, TAINA KEILLER; RIBEIRO, DIEGO LUIS; THOMAZELA MACHADO, ANA RITA; COSTA, TASSIA RAFAELA; SAMPAIO, SUELY VILELA; GREGGI ANTUNES, LUSANIA MARIA. Synephrine and caffeine combination promotes cytotoxicity, DNA damage and transcriptional modulation of apoptosis-related genes in human HepG2 cells. MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS, v. 868, . (11/23236-4, 15/00740-0, 14/20344-9)
COSTA, TASSIA R.; AMSTALDEN, MARTIN K.; RIBEIRO, DIEGO L.; MENALDO, DANILO L.; SARTIM, MARCO A.; AISSA, ALEXANDRE F.; ANTUNES, LUSANIA M. G.; SAMPAIO, V, SUELY. CR-LAAO causes genotoxic damage in HepG2 tumor cells by oxidative stress. Toxicology, v. 404, p. 42-48, . (15/00740-0, 11/23236-4, 15/00847-9)
COSTA, TASSIA R.; CARONE, SANTE E. I.; TUCCI, LUIZ F. F.; MENALDO, DANILO L.; ROSA-GARZON, NATHALIA G.; CABRAL, HAMILTON; SAMPAIO, SUELY V.. Kinetic investigations and stability studies of two Bothrops L-amino acid oxidases. Journal of Venomous Animals and Toxins including Tropical Diseases, v. 24, . (15/00740-0, 11/23236-4)
COSTA, TASSIA R.; MENALDO, DANILO L.; ZOCCAL, KARINA F.; BURIN, SANDRA M.; AISSA, ALEXANDRE F.; DE CASTRO, FABIOLA A.; FACCIOLI, LUCIA H.; GREGGI ANTUNES, LUSANIA M.; SAMPAIO, SUELY V.. CR-LAAO, an L-amino acid oxidase from Calloselasma rhodostoma venom, as a potential tool for developing novel immunotherapeutic strategies against cancer. SCIENTIFIC REPORTS, v. 7, . (15/00740-0, 11/23236-4)

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