title: Walterinnesia aegyptia venom combined with silica nanoparticles enhances the functioning of normal lymphocytes through PI3K/AKT, NFκB and ERK signaling.
abstract: BACKGROUND
  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. 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).
  
  
  RESULTS
  This 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.
  
  
  CONCLUSIONS
  Our data reveal the unique biological effects of WEV, and we demonstrated that its combination with nanoparticles strongly enhanced these biological effects.
authors.affiliation: Deanship of Scientific Research, King Saud University, P,O, Box 2454, Riyadh 11451, Saudi Arabia. badr73@yahoo.com
authors.forename: Gamal
authors.initials: G
authors.lastname: Badr
authors.forename: Mohamed K
authors.initials: MK
authors.lastname: Al-Sadoon
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: El-Toni
authors.forename: Maha
authors.initials: M
authors.lastname: Daghestani
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D054377:Chemokine CXCL12 / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D004546:Elapid Venoms / Q000494:pharmacology*; D017815:Elapidae; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D008297:Male; D051379:Mice; D008934:Mitogens / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism*; D053769:Nanocapsules / Q000737:chemistry; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D016062:Porosity; D055503:Protein Multimerization / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction; D012822:Silicon Dioxide / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; D004546:Elapid Venoms; D008934:Mitogens; D016328:NF-kappa B; D053769:Nanocapsules; D012822:Silicon Dioxide; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases