Abstract
BackgroundThe toxicity of snake venom varies over time in some species. The venom of newborn and small juvenile snakes appears to be more potent than adults of the same species, and a bite from a snake that has not fed recently, such as one that has just emerged from hibernation, is more dangerous than one that has recently fed due to the larger volume of venom injected. Therefore, the potency of a snake's venom is typically determined using the LD50 or IC50 tests. In the present study, we evaluated the anti-tumor potential of snake venom from Walterinnesia aegyptia (WEV) on the human breast carcinoma cell line MDA-MB-231, as well as its effect on the normal mice peripheral blood mononuclear cells (PBMCs).ResultsThis venom was used alone (WEV) or in combination with silica nanoparticles (WEV+NP). The IC50 values of WEV alone and WEV+NP in the MDA-MB-231 cells were determined to be 50 ng/ml and 20 ng/ml, respectively. Interestingly, at these concentrations, the venom did not affect the viability of normal human PBMCs. To investigate the in vivo effects of this venom further, three groups of mice were used (15 mice in each group): Group I was the control, Group II was subcutaneously injected with WEV, and Group III was injected with WEV+NP. Using flow cytometry and western blot analysis, we found that the blood lymphocytes of WEV-injected mice exhibited a significant increase in actin polymerization and cytoskeletal rearrangement in response to CXCL12 through the activation of AKT, NF-κB and ERK. These lymphocytes also showed a significant increase in their proliferative capacity in response to mitogen stimulation compared with those isolated from the control mice (P < 0.05). More importantly, in the WEV+NP-treated mice, the biological functions of normal lymphocytes were significantly (P < 0.05) enhanced in comparison with those of WEV-treated mice.ConclusionOur data reveal the unique biological effects of WEV, and we demonstrated that its combination with nanoparticles strongly enhanced these biological effects.
Highlights
The toxicity of snake venom varies over time in some species
In the present study, we investigated the effects of Walterinnesia aegyptia venom (WEV), alone and in combination with silica nanoparticles (WEV+NP), on the survival of a human breast carcinoma cell line (MDAMB-231) and human peripheral blood mononuclear cells (PBMCs) in vitro and the in vivo effects of WEV and Walterinnesia aegyptia venom combined with nanoparticles (WEV+NP) on mouse lymphocytes
The survival of PBMCs after treatment with up to 1 μg/ml of WEV or WEV+NP was reduced by 25%
Summary
The toxicity of snake venom varies over time in some species. The venom of newborn and small juvenile snakes appears to be more potent than adults of the same species, and a bite from a snake that has not fed recently, such as one that has just emerged from hibernation, is more dangerous than one that has recently fed due to the larger volume of venom injected. Lymphocyte proliferation is an important parameter indicating the status of the body’s migration of cells through an extracellular matrix is a multistep process that begins with the extension of lamellipodia, cell-surface protrusions comprised of actin filaments, which are anchored to the underlying substratum by small, integrin-dependent focal adhesions. In both normal and cancer cells, the polymerization of actin pushes against the plasma membrane and provides the force for forward movement. Previous studies have reported that the constitutive activation of NF-B in human melanoma cells is linked to the activation of AKT kinase, suggesting that the activation of AKT may be an early marker of tumor progression in melanoma [6] and that inhibitors of NF-B activation can block the neoplastic transformation response [7,8]
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