الفهرس 
IntroductionOnly 14 pages are availabe for public view
 |  | from | 145 |  |  |
| | | from | 145 | | |
Abstract
Liver cancer is a concerning disease that threatens people worldwide as it is the sixth from incidence and the fourth from mortality rates. In Egypt, it possesses a very advanced rank in both incidence and mortality as it is the first for men and second for women after breast cancer. Liver perform many vital processes in the body as it’s considered the body’s energy factor, help in digestion, secreting some hormones that helps in blood coagulation, so it’s impossible that man live without liver. Among the most important factors that increase the chance of developing liver cancer are infection with one of the liver viruses, especially virus B and C in addition to mycotoxins ingestion, alcohol consumption, smoking and pollution with iron and parasites. Late detection of these risk factors leads to difficulties in treatment and increase the chance of cancer occurring. The available options for liver cancer treatments whether surgical or therapeutic drugs options are fraught with restrictions and side effects that reflect on the desired results in addition to the high cost, so it was necessary to find a suitable solution to overcome these obstacles. There is a wide range of chemicals that are extracted from fruits, vegetables, and nuts. The five-ring terpenoids are considered one of those compounds that are characterized by its abundance and inexpensive preparation, in addition to having distinctive mechanisms of action as antimicrobial, anti-oxidant, anti-inflammatory and anti-cancerous cells selectively in animal models. This study was conducted to investigate the usage of several natural products and their analogs/derivatives as chemo-sensitizing agents in the treatment of liver cancer. The cytotoxicity of 36 natural product against liver cancer cell line HepG-2 was tested. The most active compounds were then furthermore investigated for their ability to inhibit cell migration and metastases using wound healing and colony assay. Compound’s safety was evaluated by calculating selective index. Flow cytometric analysis was evaluated to study the efficacy of this anti-cancer compound on cell differentiation and possible cell phase at which it induces apoptosis and possible mechanism of action. This work highlights the cytotoxicity of glycyrrhizin and its derivative for possible use as a chemotherapeutic agent against hepatocellular carcinoma cells HepG-2. Cytotoxicity results nominated both ME-GA (18β-Glycyrrhetinic-30-methyl ester) and AKBA (3-Acetyl-11-keto-β-Boswellic acid) as most cytotoxic compounds with no cytotoxic effect on the normal cell line. ME-GA has a chemo sensitizing effect through an increase in the sensitivity of HepG-2 cells to Cisplatin and Oxaliplatin. ME-GA also induced apoptosis of hepatocellular carcinoma cells HepG-2 through extrinsic pathway through an increase in expression of caspase 8 and 3 and was confirmed by an increase in the expression of P53 and an increase in Bax level, a decrease in the level of Bcl-2. In summary, this new derivative may be used as an alternative or complementary medicine for liver cancer. Recommendations: • Further studies should be done on anther liver cancer cell line Huh-7 to investigate the cytotoxic ability of those compounds on different liver cancers cells. • PCR and western blots assay to evaluate of ME-GA activity against signaling pathways in cancer. • In vivo model studies would be a good recommendation to assure the applicability of those compounds as an alternative therapeutic drug for liver cancer. • Pharmacokinetic and Pharmacodynamic study effect on metabolic, invasion and metastatic pathway.