الفهرس 
1. INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Snake venoms (SnVs) are mixture of numerous proteins and peptides,and several studies have demonstrated the therapeutic values of some bioactive compounds extracted from SnVs on various cancer cell lines as well as in some models in vivo; as cytotoxic,anti-tumor and apoptosis-inducing agents. In the current study, we evaluated the anticancer potential of crude Cerastes cerastes (C.cerastes) snake venom (SnV) alone and when conjugated with low molecular weight chitosan nanoparticels (LMWt-CSNPs) on hepatocellular carcinoma cell line HEPG2 at different concentrations and time intervals through performing MTT assay.Also,we used inverted light microscope for morphological studies, Transmission Electron Microscope (TEM) for ultrastructural investigations.Also,some measurements were carried out on chitosan nanoparticles (CSNPs) to examine their stability, surface charge and detect the appropriate size for using as a drug carrier through zetasizer instrument. We got some fundamental information about nanparticles (NPs); such as average zetapotential, average size, and polydispersity index (PDI).Nanoparticles were also examined morhologically by using TEM.Spectrophotometer analysis was carried out on SnV for qualitative and quantitative measurements.Also, it was necessary to determine the surface charge of C.cerastes venom by zetasizer before conjugation process with chitosan.The cytotoxicity of HEPG2 cells treated with free crude venom and venom-conjugated NPs of formula B (FB) was measured by MTT assay.The MTT results revealed significant cytotoxic potency of both of them, wherase there wasn’t significant cytotoxic potencyof free LMWt-CSNPs.Besides,the determined IC50 values of venom and venom-conjugated NPs were highly promising. The IC50 was 3.67 µg / ml for C.cerastes venom and 0.709 µg /ml for venom-conjugated NPs.So, the cytotoxicity of cells treated with venom-conjugated NPs appeared to be more potency than those treated with venom alone.Morphological studies and ultrastructural investigations of HEPG2 cells treated with free venom and venom-conjugated NPs at three different doses 1 ∕ 2 IC50, IC50 and 2IC50 for 1, 3, 6 and 24 hrs time intervals showed various forms of cytotoxic effect of venom on HEPG2 cells.They were in the form of: decrease in the number of filopodia,blebbing and rupture of plasma membrane,lytic necrosis,coagulative necrosis,swelling of mitochondria with cristolysis,appearance of apoptotic bodies,pyknosis,karyorrhexis and karyolysis.The data of zetapotential,size,and PDI of CSNPs and venom-conjugated NPs showed reasonable values,reflecting the stability and uniformaity of NPs.Besides,surface charge of C.cerastes venom was in negative value.The results of spectrophotometer analysis of C.cerastes venom gave absorbance peak at 278 nm,and the EE% was 75% and loading capacity was 0.2mg ⁄ mg.