Not snake oil? Antitumoral Activity of Snake Venom Proteins

Biomed Res Int. 2014;2014:203639. Epub 2014 Feb 13.

Antitumoral Activity of Snake Venom Proteins: New Trends in Cancer Therapy.

Calderon LA1, Sobrinho JC1, Zaqueo KD1, de Moura AA1, Grabner AN1, Mazzi MV2, Marcussi S3, Nomizo A4, Fernandes CF1, Zuliani JP1, Carvalho BM5, da Silva SL5, Stábeli RG1, Soares AM1.

Author information

• 1Centro de Estudos de Biomoléculas Aplicadas à Saúde, CEBio, Fundação Oswaldo Cruz, Fiocruz Rondônia e Departamento de Medicina, Universidade Federal de Rondônia, UNIR, Porto Velho, RO, Brazil.
• 2Fundação Hermínio Ometto, UNIARARAS, Núcleo de Ciências da Saúde-NUCISA, 13607-339 Araras, SP, Brazil.
• 3Departamento de Química, Universidade Federal de Lavras, UFLA, 37200-000 Lavras, MG, Brazil.
• 4Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, USP, Ribeirão Preto, SP, Brazil.
• 5Departamento de Química, Biotecnologia e Engenharia de Bioprocessos, Universidade Federal de São João del Rei, UFSJ, Campus Alto paraopeba, Ouro Branco, MG, Brazil.

Abstract

For more than half a century, cytotoxic agents have been investigated as a possible treatment for cancer. Research on animal venoms has revealed their high toxicity on tissues and cell cultures, both normal and tumoral. Snake venoms show the highest cytotoxic potential, since ophidian accidents cause a large amount of tissue damage, suggesting a promising utilization of these venoms or their components as antitumoral agents. Over the last few years, we have studied the effects of snake venoms and their isolated enzymes on tumor cell cultures. Some in vivo assays showed antineoplastic activity against induced tumors in mice. In human beings, both the crude venom and isolated enzymes revealed antitumor activities in preliminary assays, with measurable clinical responses in the advanced treatment phase. These enzymes include metalloproteases (MP), disintegrins, L-amino acid oxidases (LAAOs), C-type lectins, and phospholipases A2 (PLA2s). Their mechanisms of action include direct toxic action (PLA2s), free radical generation (LAAOs), apoptosis induction (PLA2s, MP, and LAAOs), and antiangiogenesis (disintegrins and lectins). Higher cytotoxic and cytostatic activities upon tumor cells than normal cells suggest the possibility for clinical applications. Further studies should be conducted to ensure the efficacy and safety of different snake venom compounds for cancer drug development.