Action of recombinant Bauhinia inhibitors on prostate cancer cell line. / Ação de inibidores recombinantes de Bauhinia sobre a linhagem celular de câncer de próstata.

AUTOR(ES)
DATA DE PUBLICAÇÃO

2009

RESUMO

Prostate cancer occurs in Brazil with high rates of incidence and mortality. Invasion from the primary tumor and metastasis result in poorer prognosis. Diverse classes of protein play a role for the progression of metastasis. Tissue kallikreins, e.g., hK3 (PSA) and integrins are directly related to this neoplasia, as well as, in cell adhesion, differentiation and cellular proliferation processes. Compounds that interfere in these processes are targeted for investigation. In this work, using prostate cancer cellular line PC-3, the effects of two recombinant inhibitors of Bauhinia sp. seeds were studied, the Bauhinia bauhinioides kallikrein inhibitor (rBbKI) and the modified rBbKIm, in which the signal motif RGD, present in the inhibitor BrTI from B. rufa, was inserted. The rBbKI and rBbKIm has shown different effects on cell PC3 viability, being rBbKIm more efficient than rBbKI and inhibiting 70% of PC3 cell viability (50 μM, 72h), in all the conditions analyzed. The rBbKIm has interfered in the cell cycle of PC-3, increasing the number of cells in apoptosis and decreasing the number of cells in G2 face (mitosis). In the cell adhesion, rBbKIm (25 μM), containing the adhesion motif RGD, has inhibited approximately 30% of the PC-3 adhesion on fibronectin, in contrast to rBbKI that has caused 20% of cell adhesion. The confocal microscopy analysis has shown that rBbKI and rBbKIm interact with cell membrane. The results indicate that the inhibitors act by different mechanisms, which still to be established.

ASSUNTO(S)

1. peptidase. 2. inibidor de peptidases. 3. câncer de próstata 4. integrinas 5. sequência rgd. biologia molecular

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