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Int. J. Environ. Res. Public Health 2016, 13(10), 1008; doi:10.3390/ijerph13101008

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

1
Biochemistry Department, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia
2
Biology Department, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia
*
Author to whom correspondence should be addressed.
Academic Editor: William Chi-shing Cho
Received: 16 July 2016 / Revised: 29 September 2016 / Accepted: 3 October 2016 / Published: 14 October 2016
View Full-Text   |   Download PDF [2165 KB, uploaded 14 October 2016]   |  

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. View Full-Text
Keywords: asparaginase; acute lymphoplastic leukemia; allergy; Immunogenicity; proliferation; apoptosis; cytotoxicity asparaginase; acute lymphoplastic leukemia; allergy; Immunogenicity; proliferation; apoptosis; cytotoxicity
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MDPI and ACS Style

Mohamed, S.A.; Elshal, M.F.; Kumosani, T.A.; Aldahlawi, A.M.; Basbrain, T.A.; Alshehri, F.A.; Choudhry, H. L-Asparaginase Isolated from Phaseolus vulgaris Seeds Exhibited Potent Anti-Acute Lymphoblastic Leukemia Effects In-Vitro and Low Immunogenic Properties In-Vivo. Int. J. Environ. Res. Public Health 2016, 13, 1008.

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