الفهرس 
الفصل الاولOnly 14 pages are availabe for public view
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Abstract
Hepatocellular carcinoma (HCC) is one of the most malignant tumors that affect individuals worldwide. There was significantly increased incidence of hepatocellular carcinoma during the last two decades.In Egypt, there is growing incidence of HCC (10–120/100,000), which represents the leading cause of death from all other cancer sites. RAS/MEK/ERK signal transduction pathway plays an essential role in many cellular processes, including cell proliferation, cell differentiation, and reorganization of the cytoskeleton.ERK1/2protein is a downstream component of the RAS/MEK/ERK pathway.Manuka Honey has been known for its wound-healing, anti-bacterial and antioxidant activity due to the presence of flavonoids and phenolic acid, but its potential antitumor effect is poorly studied.In the present study, we investigated thegrowth-inhibitory effect and apoptosis induction of HepG2 cells were evidenced by MTT assay, cell morphology alteration, DNA fragmentation, caspase-3 activity, expression ofproapoptotic protein, Baxand PARP cleavageafter Manuka honey (M-H) treatmentfor 48 hrs. Also anticancer effect of M-H was assessed by western blotting analysis of protein expression levels of ERK1/2,β-catenin, and cyclin D1 as a downstream signal under RAS/MEK/ERK and Wnt/β-catenin signalling pathway. Our results revealed that M-H treatment for 48 hrs showed a cytotoxic effect and apoptosis induction in a dose-dependent manner by caspase-3 activation, upregulation of Bax and PARP cleavage in HepG2 cells. On the other hand, M-H showed an inhibitory effect on ERK1/2, β-catenin and cyclin D1 expressions in HepG2 cells. Combined treatment of Manuka honey and Doxorubicin induced morphological changes, apoptosis induction and DNA fragmentation. Our data introduced M-H as a promising naturally, nontoxic product with therapeutic potential which induced apoptosis in HepG2 cells and highlight a novel role for systemically administered ofM-H as anti-cancer agentandan adjuvant in combination with standard chemotherapeutic agents as Doxorubicin.So,M-H can alleviate chemotherapy-induced toxicity.