title: L-Asparaginase Isolated from Phaseolus vulgaris Seeds Exhibited Potent Anti-Acute Lymphoblastic Leukemia Effects In-Vitro and Low Immunogenic Properties In-Vivo.
abstract: Escherichia coli-derived L-asparaginases have been used in the treatment of acute lymphoblastic leukemia (ALL), however, clinical hypersensitivity reactions and silent inactivation due to antibodies againstE. coli-asparaginase, lead to inactivation of these preparations in most cases.Therefore, this study was aimed to investigate the cytotoxicity and antitumor effects ofa novel L-asparaginaseenzyme, isolated fromPhaseolus vulgarisseeds (P-Asp) on the ALL cell line (Jurkat). The immunogenicity of the enzyme was also evaluated in-vivo and results were compared to commercially available enzymes of microbial sources. The data demonstrated that P-Asp has an enhanced anti-proliferative effect on ALL cells as detected by the WST-8 cell viability assay kit. Cells treated with P-Asp also exhibited a higher degree of early apoptosis compared with asparaginase fromEscherichia coli(L-Asp) or its pegylated form Pegasparagas (PEG-ASP) that induced higher rates of late apoptosis and necrosis as detected by an Annexin V/Propidium iodide binding assay. In-vivo experiments indicated that mice treated with P-Asp had less distinct allergenic responses than other bacterial enzyme preparations as indicated by lower serum concentrations of IgG, IgE, IgM and mMCP-1 compared with other treated groups. In conclusion, P-Asp can be considered as a promising candidate for use in the treatment of ALL.
authors.affiliation: Biochemistry Department, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia. saleh38@hotmail.com.
authors.forename: Saleh A
authors.initials: SA
authors.lastname: Mohamed
authors.affiliation: Biochemistry Department, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia. melshal2002@yahoo.com.
authors.forename: Mohamed F
authors.initials: MF
authors.lastname: Elshal
authors.affiliation: Biochemistry Department, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia. t.kumosani@yahoo.com.
authors.forename: Taha A
authors.initials: TA
authors.lastname: Kumosani
authors.affiliation: Biology Department, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia. aaldahlawi@kau.edu.sa.
authors.forename: Alia M
authors.initials: AM
authors.lastname: Aldahlawi
authors.affiliation: Biology Department, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia. dr.sema2007b@yahoo.com.
authors.forename: Tasneem A
authors.initials: TA
authors.lastname: Basbrain
authors.affiliation: Biology Department, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia. Whitemusk_at@hotmail.com.
authors.forename: Fauziah A
authors.initials: FA
authors.lastname: Alshehri
authors.affiliation: Biochemistry Department, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia. hchoudhry@kau.edu.sa.
authors.forename: Hani
authors.initials: H
authors.lastname: Choudhry
mesh_terms: D000970:Antineoplastic Agents / Q000276:immunology / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001215:Asparaginase / Q000276:immunology / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D008297:Male; D027805:Phaseolus; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D012639:Seeds
chemical_list: D000970:Antineoplastic Agents; D001215:Asparaginase
keywords: Immunogenicity; acute lymphoplastic leukemia; allergy; apoptosis; asparaginase; cytotoxicity; proliferation