Crotalus durissus terrificus  venom as a source of antitumor agents

Soares MA (1), Pujatti PB (1), Fortes Dias CL (2), Antonelli L (3), Santos RG (1)

(1) Laboratory of Radiobiology, Nuclear Technology Development Center, CDTN/CNEN, Brazil; (2) Laboratory of Biochemistry, Ezequiel Dias Foundation, Brazil; (3) Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais State, Brazil.

ABSTRACT: The basic knowledge on neoplasm is increasing quickly; however, few advances have been reached in clinical therapy of tumors. For this reason, the development of alternative drugs is relevant in the attempt to improve prognosis and to increase patients’ survival. Snake venoms are natural sources of bioactive substances with therapeutic potential. The objective of this work was to identify and to characterize the antitumor effect of Crotalus durissus terrificus venom (CV) and its polypeptide, crotoxin, on benign and malignant tumors, respectively, pituitary adenoma and glioblastoma. The results demonstrated that CV possess a powerful antitumor effect on benign (pituitary adenoma) and malignant (glioblastoma multiforme) tumors with IC₅₀ values of 0.96 ± 0.11 mcg/mL and 2.15 ± 0.2 mcg/mL, respectively. This antitumor effect is cell-cycle specific and dependent of extracellular calcium, an important factor for crotoxin phospholipase A2 activity. The CV antitumor effect can be ascribed, at least partially, to the polypeptide crotoxin that also induced brain tumor cell death. In spite of the known CV nephrotoxicity and neurotoxicity, acute treatment with its antitumor dose established in vitro was not found to be toxic for the analyzed animals. These results indicate the biotechnological potential of CV as source of pharmaceutical templates for cancer therapy.

KEY WORDS: Crotalus durissus terrificus venom, crotoxin, antitumor effect, pituitary adenoma, glioblastoma multiforme.

CORRESPONDENCE TO: 

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