Antitumoral activity of snake venom proteins: new trends in cancer therapy
Leonardo A Calderon1, Juliana C Sobrinho1, Kayena D Zaqueo1
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.
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.
Insights
Snake venoms show high cytotoxic potential against cancer cells. Research indicates their components, like metalloproteases and L-amino acid oxidases, offer promising antitumoral activity for drug development.
Area of Science:
- Biochemistry
- Pharmacology
- Oncology
Background:
- Cytotoxic agents have been explored for cancer treatment for over 50 years.
- Animal venoms, particularly snake venoms, exhibit significant toxicity to normal and tumoral cells.
- Snakebite injuries demonstrate substantial tissue damage, indicating venom's antineoplastic potential.
Purpose of the Study:
- To investigate the effects of snake venoms and their isolated enzymes on tumor cell cultures.
- To evaluate the in vivo antineoplastic activity of snake venom components.
- To explore the potential of snake venom compounds as anticancer agents in humans.
Main Methods:
- Culturing tumor cells and exposing them to crude snake venom and isolated venom enzymes.
- Conducting in vivo assays using induced tumors in mice.
- Analyzing preliminary clinical responses in human patients undergoing advanced treatment.
Main Results:
- Snake venoms and their isolated enzymes demonstrated antitumor activities in preliminary human assays.
- In vivo studies showed antineoplastic effects against induced tumors in mice.
- Specific enzymes like metalloproteases, disintegrins, L-amino acid oxidases, C-type lectins, and phospholipases A2 were identified.
Conclusions:
- Snake venom components exhibit higher cytotoxic and cytostatic effects on tumor cells than normal cells.
- Mechanisms of action include direct toxicity, free radical generation, apoptosis induction, and antiangiogenesis.
- Further research is essential to confirm the efficacy and safety of snake venom compounds for cancer drug development.
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