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Antiproliferative effect of the jararhagin toxin on B16F10 murine melanoma
Durvanei Augusto Maria1, Manuela Garcia Laveli da Silva, Mario Cesar Correia Junior
1Biochemistry and Biophysics Laboratory, Butantan Institute, Av, Vital Brasil 1500, CEP 05503-900 Sao Paulo, SP, Brazil. durvanei.maria@butantan.gov.br.
Background:
Malignant melanoma is a less common but highly dangerous form of skin cancer; it starts in the melanocytes cells found in the outer layer of the skin. Jararhagin toxin, a metalloproteinase isolated from Bothrops jararaca snake venom acts upon several biological processes, as inflammation, pain, platelet aggregation, proliferation and apoptosis, though not yet approved for use, may one day be employed to treat tumors.
Methods:
B16F10 murine melanoma cells were treated with jararhagin (jara), a disintegrin-like metalloproteinase isolated from Bothrops jararaca snake venom, and jari (catalytic domain inactivated with 1,10-phenanthroline). Viability and adhesion cells were evaluated by MTT assay. The expression of caspase-3 active, phases of the cell cycle and apoptosis were assessed by flow cytometry. We analyze in vivo the effects of jararhagin on melanoma growth, apoptosis and metastasis.
Results:
The tumor cells acquired round shapes, lost cytoplasmic expansions, formed clusters in suspension and decreased viability. Jari was almost 20 times more potent toxin than jara based on IC50 values and on morphological changes of the cells, also observed by scanning electron microscopy. Flow cytometry analysis showed 48.3% decrease in the proliferation rate of cells and 47.2% increase in apoptosis (jara) and necrosis (jari), following 1.2 μM jara and 0.1 μM jari treatments. Caspase-3 activity was increased whereas G0/G1 cell cycle phase was on the decline. Proliferative rate was assessed by staining with 5,6-carboxyfluoresceindiacetate succinimidyl ester, showing a significant decrease in proliferation at all concentrations of both toxins.
Conclusions:
In vivo treatment of the toxins was observed reduction in the incidence of nodules, and metastasis and antiproliferative inhibition capacity. This data strengthens the potential use jararhagin as an anti-neoplastic drug.
Insights
Jararhagin toxin from snake venom shows potential as an anti-cancer drug. It effectively reduced melanoma cell proliferation, induced apoptosis, and inhibited tumor growth and metastasis in vivo.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Malignant melanoma is a dangerous skin cancer originating in melanocytes.
- Jararhagin, a snake venom metalloproteinase, influences biological processes like proliferation and apoptosis.
- Jararhagin shows potential for future anti-tumor therapies.
Purpose of the Study:
- To investigate the anti-cancer effects of jararhagin and its derivative jari on melanoma.
- To evaluate the impact of these toxins on cell viability, proliferation, apoptosis, and metastasis in vitro and in vivo.
Main Methods:
- Murine melanoma cells (B16F10) treated with jararhagin (jara) and inactivated jari.
- Assessed cell viability, adhesion, proliferation, cell cycle, and apoptosis using MTT assay and flow cytometry.
- Evaluated in vivo effects on tumor growth, apoptosis, and metastasis.
Main Results:
- Jararhagin and jari induced morphological changes, decreased cell viability, and reduced proliferation.
- Jari was significantly more potent than jara.
- Toxins increased caspase-3 activity, decreased G0/G1 phase, and promoted apoptosis/necrosis.
- In vivo studies showed reduced tumor nodules and metastasis.
Conclusions:
- Jararhagin demonstrates significant antiproliferative and anti-metastatic effects.
- The data supports jararhagin's potential as an anti-neoplastic drug.
- Further research into jararhagin as a cancer therapeutic is warranted.
