In vitro evaluation of therapeutic potential of single and combined effect of Snake venom, its active ingredient L-amino acid oxidase and Sorafenib in Hepatocellular carcinoma / Dalia Hesham Naguib Mahfouz ; Supervised Ismail Abdelshafy Abdelhamid , Emad Mahmoud Elzayat , Abdelhady Ali Abdelwahab

Thesis (M.Sc.) - Cairo University - Faculty of Science - Department of Biotechnology

Background: Sorafenib (SOR) is the only approved molecular targeted agent for the hepatocellular carcinoma (HCC) treatment. However, its use is delayed by the recently articulated safety concerns. One approach to reduce SOR toxicity is to use lower doses in combination with less toxic agents. Snake venoms (SVs) and their active ingredients especially L-amino acid oxidase (svLAAO) have shown cytotoxic effects on different cell lines and exhibited high selectivity to cancer cells. However, the mechanisms of action of these ingredients are still to be clarified. Aim of study: the present study aimed to test the hypothesis that combining snake venom (SV) or L- amino acid oxidase (svLAAO) could synergistically enhance the anti-proliferative effects of SOR in HepG2 cells versus normal liver cells (THLE-2) at low doses; test the efficiency of crude SV from the Egyptian viber (Cerastes cerastes) against and active ingredient svLAAO (western black rattlesnake) in human hepatocellular carcinoma cell line (HepG2) versus normal human liver cells (THLE-2); investigate the underlying mechanisms for such combination on proliferation , apoptosis and cell cycle; evaluate of the oxidant/antioxidant status in HepG2 cells as affected by different regimens of crude SV, svLAAO, and Sorafenib.; test the cytotoxic efficiency and intracellular immune modulation of SV versus its active ingredient svLAAO in combination with SOR and to speculate the underlying mechanism for such combinationscancer cell line

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