Análise antitumoral e antiagregante da Bothalternina: uma toxina purificada da peçonha da serpente Bothrops alternatus

Abstract

Snakes venoms are a complex mixture of proteins, organic and inorganic compounds. Some of the protein, enzymatic or non-enzymatic compounds are able to interact with platelet receptors, causing hemostatic disorders such as blood incoagulability, hemorrhage and thrombosis, as well as to interact with components of the extracellular matrix, activating or inhibiting cell growth. Because of its medical importance, these compounds acting on hemostasis have been isolated from the venom of snakes and studied as potential therapeutic in the treatment and diagnosis of diseases such as thrombosis and cancer. The present study aimed to purify and to characterize a toxin present in the venom of Bothrops alternatus. The toxin called Bothalternina was purified using columns size ion-exchange on DEAE-Sephacel and Reversed Phase (C2/C18). The analysis of two-dimensional electrophoresis showed that Bothalternina has an apparent molecular mass of 26 kDa and pI to 4.6. The amino acid sequence of the N-terminal region was carried out by Edman degradation method and revealed the following sequence: (IISPPVCGNELLEVGEECDCGTPENCQNECCDA), which showed identity with the PIII class SVMPs. Bothalternina had a specific inhibitory effect on platelet aggregation induced by ristocetin in platelet rich human plasma. On the other hand, the toxin did not inhibit the ADP and epinephrine-induced aggregation. Bothalternina was also able to inhibit the growth of HeLa tumor cells. This toxin can be of medical interest because it was shown to inhibit platelet aggregation and tumor cell growth.