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Toad Venom Antiproliferative Activities on Metastatic Melanoma: Bio-Guided Fractionation and Screening of the
Laura Soumoy1, Mathilde Wells2, Ahmad Najem3
1Laboratory of Human Anatomy and Experimental Oncology, Faculty of Medicine and Pharmacy, University of Mons, 7000 Mons, Belgium.
Abstract:
Melanoma is the most common cancer in young adults, with a constantly increasing incidence. Metastatic melanoma is a very aggressive cancer with a 5-year survival rate of about 22-25%. This is, in most cases, due to a lack of therapies which are effective on the long term. Hence, it is crucial to find new therapeutic agents to increase patient survival. Toad venoms are a rich source of potentially pharmaceutically active compounds and studies have highlighted their possible effect on cancer cells. We focused on the venoms of two different toad species: Bufo bufo and Rhinella marina. We screened the venom crude extracts, the fractions from crude extracts and isolated biomolecules by studying their antiproliferative properties on melanoma cells aiming to determine the compound or the combination of compounds with the highest antiproliferative effect. Our results indicated strong antiproliferative capacities of toad venoms on melanoma cells. We found that these effects were mainly due to bufadienolides that are cardiotonic steroids potentially acting on the Na+/K+ ATPase pump which is overexpressed in melanoma. Finally, our results indicated that bufalin alone was the most interesting compound among the isolated bufadienolides because it had the highest antiproliferative activity on melanoma cells.
Insights
Toad venoms show significant antiproliferative effects against melanoma cells. Bufalin, a compound found in toad venom, demonstrated the highest potential for treating this aggressive cancer.
Area of Science:
- Pharmacology
- Oncology
- Biochemistry
Background:
- Melanoma incidence is rising, particularly in young adults.
- Metastatic melanoma has a poor prognosis due to limited effective long-term therapies.
- New therapeutic strategies are urgently needed to improve patient survival rates.
Purpose of the Study:
- To investigate the antiproliferative effects of toad venoms on melanoma cells.
- To identify specific compounds within toad venoms responsible for anti-melanoma activity.
- To evaluate the potential of toad venom components as novel anti-melanoma agents.
Main Methods:
- Screening of crude extracts, fractions, and isolated biomolecules from *Bufo bufo* and *Rhinella marina* toad venoms.
- Assessment of antiproliferative properties on melanoma cell lines.
- Identification of active compounds, focusing on bufadienolides.
Main Results:
- Toad venom extracts exhibited significant antiproliferative activity against melanoma cells.
- Bufadienolides were identified as the primary active components.
- Bufalin demonstrated the highest antiproliferative efficacy among the isolated bufadienolides.
Conclusions:
- Toad venoms possess potent anti-melanoma properties.
- Bufadienolides, particularly bufalin, represent promising therapeutic leads for melanoma treatment.
- Targeting the Na+/K+ ATPase pump, overexpressed in melanoma, may be a key mechanism of action.
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