Antiproliferative effect of the jararhagin toxin on B16F10 murine melanoma

Abstract

BackgroundMalignant 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.MethodsB16F10 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.ResultsThe 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.ConclusionsIn 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.

Bothrops jararaca and Bothrops erythromelas Snake Venoms Promote Cell Cycle Arrest and Induce Apoptosis via the Mitochondrial Depolarization of Cervical Cancer Cells

“…Previous trials have reported that snake venoms are able to act on the tumor in some models, such as melanoma (B16F10 cells) [21], breast (MCF-7 cells) [22], colon (HCT116 and HT-29 cells) [23], lung cancer (NCL-H460 cells) [24], and neuroblastoma (SK-N-MC and SK-N-SH cells) [25]. However, despite these data, there are few studies relating to Bothrops in cervical cancer cell lines.…”

Purification of a fragment obtained by autolysis of a PIIIb-SVMP from Bothrops alternatus venom

“…demonstrated using jararhagin inactivated with 10 mM 1,10-phenanthroline [31]. Thereby, it is probable that both baltergin and baltergin-DC are able to interact with surface integrins impairing C2C12 adhesion to coated plate.…”

Effects of Animal Venoms and Toxins on Hallmarks of Cancer

“…Anticancer activities of SVMPs involve pro-inflammatory effect and apoptotic activity. A purified SVMP from Bothrops jararaca , Jararhagin, interrupted cancer cell adhesion and exhibited a potent cytotoxic effect on melanoma cells 21 via an increase in caspase-3 and anti-proliferative activities 22 . A metalloproteinase from Trimeresurus stejnegeri venom, TSV-DM, inhibited cancer cell proliferation and induced morphological changes on ECV304 cells 23 .…”