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
• Start date: May 01, 2015
• End date: 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

Abstract

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.

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)

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, DEC 4 2018. (15/00740-0, 11/23236-4)

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, AUG-SEP 2021. (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, JUL 1 2018. (15/00740-0, 11/23236-4, 15/00847-9)

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, FEB 16 2017. (15/00740-0, 11/23236-4)

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, MAR 11 2020. (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)

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, OCT 2017. (15/00740-0, 11/23236-4, 15/25637-7)

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, MAY 2018. (15/00740-0, 15/26609-7, 16/20641-9, 11/23236-4)

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, DEC 20 2018. (15/00740-0, 15/25637-7, 11/23236-4, 14/04234-9)