الفهرس 
AbstractOnly 14 pages are availabe for public view
 |  | from | 251 |  |  |
| | | from | 251 | | |
Abstract
Nowadays, Sorafenib is one of the approved (HCC) systemic chemotherapy, however, it still faces many problems including resistance and toxic effects related to the required dose. Amygdalin possesses anticancer activities against several cancer cell lines. This study used both in vitro experiments and in silico molecular docking methods to investigate amygdalin/Sorafenib’s probable synergistic effect in targeting AMPK/mTOR signaling pathway and their effects on apoptosis and autophagy in HepG2 cells. Amygdalin showed cytotoxic selectivity against the HepG2 cells compared to the normal WI-38 cells (IC50 = 5.21 mg/ml; 141.25 mg/ml, respectively) which was more sensitive to the toxicity by sorafenib. Amygdalin/Sorafenib combination showed strong synergism (CI50 = 0.56), which was associated with arresting cell cycle at the S and G2/M phases and enhancing apoptosis and necrosis. Amygdalin/Sorafenib co-treatment elevated glutathione and attenuated MDA levels, as well as increased the expression levels for the pro-autophagic genes AMPK, HGMB1, ATG5, Beclin 1, and LC3 while decreasing the mTOR, and BCL2 anti-apoptotic gene expression. Finally, the molecular docking study showed that Amygdalin enhanced the activity of AMPK by binding to the active site of its inhibitors, causing inactivation of theses enzymes that down-regulate its activity. This activation of AMPK inhibited mTOR thus provoking apoptosis in the HepG2 cells.