الفهرس 
These mechanisms will be evaluated through measuring;Only 14 pages are availabe for public view
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Abstract
Hepatocellular carcinoma (HCC) is the most common primary hepatic tumor and the fifth most common tumor worldwide. HCC is one of the leading causes of cancer deaths in Asia and Africa. The HCC 5-year survival rate is less than 5 percent without treatment. Any chronic inflammatory liver disease has the potential to induce HCC, but the pathophysiological process found in up to 80 percent of cases of the disease is cirrhosis. Approximately 90 to 95 percent of tumors are the biologic consequences of persistent hepatitis B virus (HBV) and hepatitis C virus (HCV) infections.
Apoptosis is one of the main types of programmed cell death which involves a series of biochemical events leading to specific cell morphology characteristics and ultimately death of cells. Apoptosis differentiates from necrosis as the processes associated with apoptosis in disposal of cellular debris do not damage the organism in apoptosis. Apoptosis plays a role in preventing cancer; if a cell is unable to undergo apoptosis, due to mutation or biochemical inhibition, it can continue dividing and develop into a tumor.
Oxidative stress is caused by an imbalance between the production of reactive oxygen and nitrogen species (ROS and RNS) and a biological system’s ability to readily detoxify these reactive intermediates or easily repair the resulting damage. Disturbances in the normal redox state within the cells can cause toxic effects that damage all components of the cell, including proteins, lipids, and DNA, this massive cell damage can result in cellular mutations, tissue breakdown and immune compromise.
Moreover oxidants can act at several stages of malignant transformation, where ROS generated chemically or enzymatically, play an important role in initiation, promotion and progression of multi stage carcinogenesis.
The aim of the present study was to evaluate the in vitro antineoplastic effect of Nigella sativa and bee honey on hepatocellular carcinoma cells and to clarify the molecular and biochemical mechanisms which could be involved in their effects. These mechanisms could be related to their antioxidant and/or apoptotic activities.
Human liver cancer cell line (HepG2) was used in this study. It was maintained in culture using standard cell culture techniques. Following cellular growth to 90% confluencey, exposure of the cell line to different concentrations of diluted unfractionated bee honey (BH) (5%, 10%, 15% and 20%), and to different doses of alcohol extract of Nigella sativa(NS) (1000µg/ml, 2500µg/ml and 5000µg/ml) and their mixtures (Mix 1 (BH 15% and NS 2500µg/ml), Mix 2 (BH 20% and NS 5000µg/ml)) at different time intervals (6 hrs, 24 hrs, 48 hrs, 72 hrs) was performed.
HepG2 cells (2x106 cell/ T-25 culture flask) were treated with BH, NS and Mix 1, 2 in duplicates in T-25 culture flasks. The antiproliferative activity of BH and NS was assessed by trypan blue exclusion viability test followed by calculating the cell survival percentage under various concentrations and mixtures at different time intervals. The antioxidant activities of BH and NS were assessed by determination of the cyclooxygenase-2 (COX-2) expression in culture cell pellet.
Moreover, the apoptotic effects of BH and NS were evaluated by measuring the change in the levels of Transforming growth factor-β1 (TGF-β1) in culture supernatant as an upstream signal of apoptosis and assessment of the downstream signals by measuring Cytochrome c levels in culture cell lysate. All assays were performed in both untreated HepG2 cells as a control and treated HepG2 cells, with BH, NS and Mix1, 2 to evaluate their antineoplastic activities by comparing both groups.