| Naja haje L-amino acid oxidase: A selective cytotoxic enzyme against hepatocellular carcinoma |
| Paper ID : 1029-ISCBAS |
| Authors |
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Walaa Hussein Salama *1, Roqaya Ibrahim Bassuiny2, Ahmed A Abd-Rabou3 1Molecular biology dept.,NRC 2Molecular Biology dept., NRC 3Hormones dept., NRC |
| Abstract |
| Presently, cancer and antibiotic-resistant bacteria are major global human health issues. A seek for finding alternative therapeutics rather than the current one, particularly from natural sources, has become fundamental. Snake venom is an endless treasure of bioactive compounds that have different pharmacological effects. Thus, the aim of this study is to purify L-amino acid oxidase from venom of Egyptian cobra, one of the most dangerous snakes present in Egypt, as well as biochemically characterize the purified enzyme and study its antitumor effect against hepatocellular carcinoma cell lines. A homodimeric L-amino acid oxidase with a molecular mass of approximately 70 kDa was purified by a two-step sequential chromatography protocol and 25-fold purification over the whole venom. The LAAO has high substrate specificity towards L-Arg, L-Met and L-Leu. It has an optimal pH and temperature of 8 and 37 oC, respectively. It exhibited antibacterial activity against the tested strains. E. coli and Gentamicin-resistant P. aeruginosa are the most susceptible strains with MICs of 18±2 µg/mL. Additionally, LAAO inhibited the proliferation of HepG2 and Huh-7 cells with IC50 of 79.37 and 60.11 µg/mL, respectively, and had a minimal effect on WI-38 cells. Consequently, the apoptosis % of the LAAO-treated HepG2 and Huh-7 cells were 12±1 and 34.5±2.5 %, respectively. Further, it arrested the cell cycle of HepG2 and Huh7 cells in the G0/G1 phase. The findings demonstrate the powerful selective cytotoxicity of L-amino acid oxidase against tumor cells which opens up the possibility of being a good candidate for clinical cancer therapy. |
| Keywords |
| Venom; L-amino acid oxidase; Purification; Antibacterial; Cytotoxicity; Apoptosis |
| Status: Abstract Accepted (Oral Presentation) |