L-Asparaginase Isolated from Phaseolus vulgaris Seeds Exhibited Potent Anti-Acute Lymphoblastic Leukemia Effects In-Vitro and Low Immunogenic Properties In-Vivo

Saleh A. Mohamed, Mohamed F. Elshal, Taha A. Kumosani, Alia M. Aldahlawi, Tasneem A. Basbrain, Fauziah A. Alshehri and Hani Choudhry
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Saleh A. Mohamed: Biochemistry Department, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia
Mohamed F. Elshal: Biochemistry Department, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia
Taha A. Kumosani: Biochemistry Department, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia
Alia M. Aldahlawi: Biology Department, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia
Tasneem A. Basbrain: Biology Department, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia
Fauziah A. Alshehri: Biology Department, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia
Hani Choudhry: Biochemistry Department, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia

IJERPH, 2016, vol. 13, issue 10, 1-10

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 against E. 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 from Phaseolus vulgaris seeds (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 from Escherichia 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.

Keywords: asparaginase; acute lymphoplastic leukemia; allergy; Immunogenicity; proliferation; apoptosis; cytotoxicity (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2016
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