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PALOMINO RODRIGUEZ M. G. Evaluation of antitumor effects of ophidic metalloproteinase jararhagin in breast adenocarcinoma. 2012. 171 p. Masters thesis (Biothecnology) – Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, 2012. Jararhagin is a metalloproteinase from the venom of Bothrops jararaca, able to change various functions in experimental models, such as homeostasis, coagulation, inflammation, cell migration, cytokine release, proving to be an antiproliferative and pro-apoptotic potential agent in tumor cells. In this work, we have studied the in vitro effects of jararhagin in MCF7 and T47D human and murine (“Ehrlich tumor”) breast tumor cellular models, and normal fibroblast and endothelial cells. We assessed cell viability, morphological changes, cell cycle phases alterations and cell death. The in vivo effects were performed on murine model of Ehrlich ascitic and solid-orthotopic carcinoma in BALB / c mice. The in vitro results showed that jararhagin significantly decreases cell viability and adherence to the substrate in a dose dependent manner. Morphologically, were detected the formation of multicellular aggregates in the supernatant, spheroids structures and tubulo-acinar formation in breast human tumor cells, activating mechanisms of survival in human breast tumor cells, whereas murine adenocarcinoma cells showed sensitivity to the toxin, and the normal cells showed apoptosis death. The treatment in vivo showed increased inflammatory infiltrate and systemic immune response, with a left shift. The antitumor parameters showed no decrease in tumor volume present in the abdominal cavity in ascites tumor model, however, the orthotopic model, the Jararhagin induces exacerbation of local inflammatory response, and intense remodeling of extracellular matrix, with changes in the distribution and organization of the fibers collagen. It is concluded that jararagina induces cytotoxicity in tumor cell lines and normal breast. In vivo, the treatment of animals bearing Ehrlich tumor, the jararhagin not reduce tumor volume, but was able to induce systemic inflammation intratumoral and stimulation with distinct modulatory effects along the growth and dissemination of tumor cells.

Avaliação dos efeitos antitumorais da metaloproteinase ofídica jararagina no adenocarcinoma de mama.