الفهرس 
IntroductionOnly 14 pages are availabe for public view
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Abstract
Liver cancer is considered as the seventh most common cancer and the fourth leading cause of cancer deaths around the world, For Egypt it is the 1st common cancer and the 1st leading cause of cancer deaths. Recently, Drug based natural products have provided chances for the development of various antitumor molecule. DOx also has been regarded as one of the effective chemotherapy drugs for cancer treatment. Its main mechanisms of action lead to the activation of apoptotic pathways and are intercalation into DNA, inhibition of topoisomerase II, and generation of reactive oxygen species. In present study, Methylene chloride, ethyl acetate, Petroleum ether, methanol, Aqueous and n-Butanol were used for the successive extraction of phytochemicals present in olive leaves which considered as promising agents for the clinical treatment of liver cancer. Antioxidant activities were measured in ipophilic and hydrophilic extracts of Olive leave with four assays which are DPPH (2, 2’-Diphenyl-1- picrylhydrazyl assay), ABTS (2, 2’-azino-bis [3-thylbenzothiazoline-6-sulphonic acid] assay), GPX (Glutathione peroxidase assay) and SOD (Superoxide dismutase assay) in which the fractions of the methanolic extract of OLE reflect their radical scavenging properties and all the results were compared with the standard ascorbic acid. The results of these assays reveal that the most potent radical scavenging properties of fractions are ethyl acetate, crude, n-butanol and methylene. Cl. This indicates that the fractions of olive leave extract have the ability for damaging the oxidation by products and act as antioxidant agent. The anticancer potential activity for the fractions of the methanolic extract of OLE and the combination with DOx was detected by MTT assay, IC50 values which are the measure of effectiveness of a substance in inhibiting a specific biological reaction, also detection of ROS wad carried out as a mean to measure the anticancer activity. The results for MTT assay and detection of ROS showed that the highest cytotoxic effect that lead to the highest inhibitory effect to the growth and viability of HepG2 cells and the lowest concentration of ROS generated was when the cells treated with a combination pte.ether and dox with cytotoxicity of 83.82% and ROS concentration 28U/ml followed by when the cells treated with a combination methylene.cl and dox with cytotoxicity of 80.41% and ROS concentration 30U/ml. The fractions with highest anticancer activity pte.ether and methylene chloride and their combination with DOx were further examined to find their effect on gene expression of glypcan-3 as a biomarker for HCC through using Quantitative Real-Time PCR all the results compared to control of untreated cells. The results showed that when the HepG2cells treated by pte.ether combined with dox, the expression of (GPC3) is highly decreased to (gene expression fold (2^-ΔΔCt) 1.2) more than when treated with methylene combined with dox with (gene expression fold (2^-ΔΔCt) 1.1).Apoptosis induction as a mean for the anticancer activity was determined for the fractions with highest anticancer activity pte.ether and methylene chloride and their combination with DOx using flow cytometric cell cycle analysis with propidium iodide PI. The results showed that the highest apoptosis induction when the cells treated with a combination of Dox and pte.ether followed by the combination between Dox and methylene chloride this reveals that these fractions has strong anticancer activity. Apoptosis induction was again determined for the fractions with highest anticancer activity pte.ether and methylene chloride and their combination with DOx but this time through using apoptotic protein Bax, Bcl2 and P53 elisa kits all the results compared to control of untreated cells. The results showed that, in the treated HepG2 cells the concentration of bax (pro-apoptotic) was increased, the concentration of bcl2 (anti-apoptotic) was decreased and the concentration of P53 (induce apoptosis) was increased.All of these highly induce apoptosis of cell and this reveal the cytotoxic effect of the treatments. The action level for these results was as follow combination between Dox and pte.ether, combination between Dox and methylene chloride, pte.ether, methylene chloride and DOx. All investigations and results prove that the fractions of methanolic extract of OLE especially pte.ether and methylene chloride fractions can act as anti-liver cancer. Therefore, we can say that we have the chance to develop a new antitumor drug as Drug based natural products.