The effect of montivipera bornmuelleri venom on B16 and MCA cell lines and on the tumor size in mice

Abstract

Several types of venoms from animals such as snakes, scorpions, and bees are being tested for their therapeutic potentials. Montivipera bornmuelleri is a Lebanese snake whose venom has been shown to have immunomodulatory effects and anti-tumoral activities. Previous studies showed that it can induce the up-regulation of many cytokines such as INF-γ, TNF-α, IL-1β, IL-4, IL-17 most of which are known to mainly be proinflammatory and the down-regulation of the anti-inflammatory one IL-10. In addition, this venom was shown to have selective cytotoxic activities on keratinocytes cancer cells in a dose dependent manner. However, the in vivo anti-cancer actions have not been yet studied. In this study, the sensitivity of the murine cancer cell lines B16-F10, B16-OVA, MCA-Mock, and MCA-OVA to M. bornmuelleri venom was investigated. First, the concentration of proteins, which are the major active components of the venom was identified. Also, to exclude any source of error due to endotoxin contaminations, EndoLISA was performed showing the absence of bacterial LPS. Thereafter, the toxicity of different venom concentrations on the different cell lines was assessed using the Flow Cytometry cell counting and the XCelligence Assays showing a dose dependent cell death. The results showed that the B16-OVA cell line is the most sensitive to the venom. On the other hand, mice were subcutaneously injected with different venom concentration showing that 100 g/kg is the optimal non-necrotic venom dosage. B16-OVA cells were injected subcutaneously on both sides of the mice abdomen and the right side was then treated with 100 g/kg of the venom and the tumor size was measured for 33 days showing no tumor regression as compared to the negative and positive controls. Thus although the venom has shown promising in vitro toxicity on cancer cell lines, further in vivo studies using different doses and cancer models should be conducted to determine any anti-cancer potential of this venom and the related mechanism of action.