Veneno da formiga Dinoponera quadriceps como fonte de peptídeos bioativos

• Ano de defesa: 2018
• Autor(a) principal: Lima, Danya Bandeira
• Orientador(a): Martins, Alice Maria Costa
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Palavras-chave em Português: Neoplasias; Trypanosoma cruzi; Doença de Chagas
• Link de acesso: http://www.repositorio.ufc.br/handle/riufc/30045

Antimicrobial peptides have antibacterial, antiparasitic and antitumor properties. Dinoponera quadriceps ant venom (DqV) is rich in antimicrobial peptides called dinoponeratoxins (Dntxs) and it has antimicrobial and trypanocidal properties. Searching for novel trypanocidal and antitumor agents, we evaluated the antichagasic effect of DqV, Dntxs (sDq-3348, sDq-2561, sDq-1503, sDq-1319) and its fragment sDq-2561[12-23], as well the antitumor effect of Dntxs on breast and cervical cancer strains. The trypanocidal effect was evaluated in epimastigote, trypomastigote and amastigote forms of Y strain of Trypanosoma cruzi (benznidazole-resistant strain). Toxicity was assessed in the host cells LLC-MK2 by MTT and the selectivity index (SI) was determined. The action mechanism in T. cruzi was evaluated in epimastigote forms by flow cytometry using the 7AAD/AX, DCF, Rho 123 and acridine orange markers and by scanning electron microscopy (SEM). The antitumor effect was evaluated in breast cancer (MDA-MB-231, MDA-MB-468, MCF7) and cervical cancer (HeLa) by MTS. Toxicity in normal ovarian lineage (MCF10A) was also measured by MTS. The antitumor mechanism of action was evaluated by time-lapse microscopy with AX and PI labeling and LDH release assay. DqV was able to inhibit amastigote forms of T. cruzi showing an IS of 112, acting by necrotic and apoptotic mechanisms. sDq-2561 and sDq-3348 were able to inhibit epimastigote, tripomastigote and amastigote forms of T. cruzi. sDq-2561 showed similar effect of DqV and a necrotic mechanism. Dq-3348 showed apoptotic mechanism with no evidence of autophagy. In the antitumor assay, sDq-3348 showed effect against MDA-MB-468 and HeLa, but sDq-3348 was not selective. sDq-2561 demonstrated effect on MDA- B-231 and HeLa by necrotic mechanism with maximum effect at two hours of incubation. None of the Dntxs tested was cytotoxic to MCF10A. sDq-1319, sDq-1503 and sDq-2561 [12-23] showed no promising antitumor or trypanocidal effects.