Walterinnesia aegyptia venom combined with silica nanoparticles enhances the functioning of normal lymphocytes through PI3K/AKT, NFκB and ERK signaling

Lipids in Health and Disease

Maha Daghestani³  Ahmed M El-Toni¹  Mohamed K Al-Sadoon³  Gamal Badr² 

[1] King Abdullah Institute for Nanotechnology, King Saud University, Riyadh, Saudi Arabia;Zoology Department, Faculty of Science, Assiut University, 71516 Assiut, Egypt;Zoology Department, College of Science, King Saud University, Riyadh, Saudi Arabia

关键词: Snake venom;    Cell signaling;    Proliferation;    Nanoparticles;    Lymphocytes;    Growth arrest;    Cytoskeleton;   

Others  :  1160352
DOI  :  10.1186/1476-511X-11-27

 received in 2012-01-09, accepted in 2012-02-15,  发布年份 2012

【 摘 要 】

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.

Conclusion

Our data reveal the unique biological effects of WEV, and we demonstrated that its combination with nanoparticles strongly enhanced these biological effects.

【 授权许可】

   
2012 Badr et al; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Liu SZ: Radiation-induced change in lymphocyte proliferation and its neuroendocrine regulation: dose-response relationship and pathophysiological implications. Nonlinearity Biol Toxicol Med 2004, 2:233-243.
• [2]Datta S, Sarvetnick N: Lymphocyte proliferation in immune-mediated diseases. Trends Immunol 2009, 30:430-438.
• [3]Ridley AJ, Schwartz MA, Burridge K, Firtel RA, Ginsberg MH, Borisy G, Parsons JT, Horwitz AR: Cell migration: integrating signals from front to back. Science 2003, 302:1704-1709.
• [4]Wozniak MA, Modzelewska K, Kwong L, Keely PJ: Focal adhesion regulation of cell behavior. Biochim Biophys Acta 2004, 1692:103-119.
• [5]Kohno M, Pouyssegur J: Targeting the ERK signaling pathway in cancer therapy. Ann Med 2006, 38:200-211.
• [6]Yang J, Richmond A: Constitutive IkappaB kinase activity correlates with nuclear factor-kappaB activation in human melanoma cells. Cancer Res 2001, 61:4901-4909.
• [7]Wang CY, Cusack JC Jr, Liu R, Baldwin AS Jr: Control of inducible chemoresistance: enhanced anti-tumor therapy through increased apoptosis by inhibition of NF-kappaB. Nat Med 1999, 5:412-417.
• [8]Ferlay J, Bray F, Pisani P, Parkin DM: GLOBOCAN 2000: Cancer Incidence, Mortality and Prevalence Worldwide. IARC Cancer Base No. 5. [1.0]. Lyon, France: IARC; 2001.
• [9]Kuete V, Wabo HK, Eyong KO, Feussi MT, Wiench B, Krusche B, Tane P, Folefoc GN, Efferth T: Anticancer activities of six selected natural compounds of some Cameroonian medicinal plants. PLoS One 2011, 6:e21762.
• [10]Francis S, Markland A: Novel S nake venom disintegrin that inhibits human ovarian cancer dissemination and angiogenesis in an orthotopic nude mouse model. Haemostasis 2001, 31:183-191.
• [11]Barratt G: Colloidal drug carriers: achievements and perspectives. Cell Mol Life Sci 2003, 60:21-37.
• [12]Badr G, Borhis G, Treton D, Moog C, Garraud O, Richard Y: HIV type 1 glycoprotein 120 inhibits human B cell chemotaxis to CXC chemokine ligand (CXCL) 12, CC chemokine ligand (CCL)20, and CCL21. J Immunol 2005, 175:302-310.
• [13]Alama A, Bruzzo C, Cavalieri Z, Forlani A, Utkin Y, Casciano I, Romani M: Inhibition of the nicotinic acetylcholine receptors by cobra venom α-neurotoxins: is there a perspective in lung cancer treatment? PLoS One 2011, 6:(6):e20695.
• [14]Park MH, Son DJ, Kwak DH, Song HS, Oh KW, Yoo HS, Lee YM, Song MJ, Hong JT: Snake venom toxin inhibits cell growth through induction of apoptosis in neuroblastoma cells. Arch Pharm Res 2009, 32:1545-1554.
• [15]Yamazaki D, Kurisu S, Takenawa T: Regulation of cancer cell motility through actin reorganization. Cancer Sci 2005, 96:379-386.
• [16]Oliva IB, Coelho RM, Barcellos GG, Saldanha-Gama R, Wermelinger LS, Marcinkiewicz C, Benedeta Zingali R, Barja-Fidalgo C: Effect of RGD-disintegrins on melanoma cell growth and metastasis: involvement of the actin cytoskeleton, FAK and c-Fos. Toxicon 2007, 50:1053-1063.
• [17]Rao J, Li N: Microfilament actin remodeling as a potential target for cancer drug development. Curr Cancer Drug Targets 2004, 4:345-354.
• [18]Badr G, Borhis G, Lefevre EA, Chaoul N, Deshayes F, Dessirier V, Lapree G, Tsapis A, Richard Y: BAFF enhances chemotaxis of primary human B cells: a particular synergy between BAFF and CXCL13 on memory B cells. Blood 2008, 111:2744-2754.
• [19]Karin M, Greten FR: NF-kappaB: linking inflammation and immunity to cancer development and progression. Nat Rev Immunol 2005, 5:749-759.
• [20]Ding M, Kisin ER, Zhao J, Bowman L, Lu Y, Jiang B, Leonard S, Vallyathan V, Castranova V, Murray AR, Fadeel B, Shvedova AA: Size-dependent effects of tungsten carbide-cobalt particles on oxygen radical production and activation of cell signaling pathways in murine epidermal cells. Toxicol Appl Pharmacol 2009, 241:260-268.
• [21]Chung CH, Wu WB, Huang TF: Aggretin, a snake venom-derived endothelial integrin alpha 2 beta 1 agonist, induces angiogenesis via expression of vascular endothelial growth factor. Blood 2004, 103:2105-2113.