L-Asparaginase Isolated from Phaseolus vulgaris Seeds Exhibited Potent Anti-Acute Lymphoblastic Leukemia Effects In-Vitro and Low Immunogenic Properties In-Vivo
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, thi...
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doaj-546eb20ce6c84c5ebd8260f67c9393412020-11-24T22:24:43ZengMDPI AGInternational Journal of Environmental Research and Public Health1660-46012016-10-011310100810.3390/ijerph13101008ijerph13101008L-Asparaginase Isolated from Phaseolus vulgaris Seeds Exhibited Potent Anti-Acute Lymphoblastic Leukemia Effects In-Vitro and Low Immunogenic Properties In-VivoSaleh A. Mohamed0Mohamed F. Elshal1Taha A. Kumosani2Alia M. Aldahlawi3Tasneem A. Basbrain4Fauziah A. Alshehri5Hani Choudhry6Biochemistry Department, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi ArabiaBiochemistry Department, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi ArabiaBiochemistry Department, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi ArabiaBiology Department, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi ArabiaBiology Department, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi ArabiaBiology Department, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi ArabiaBiochemistry Department, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi ArabiaEscherichia 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.http://www.mdpi.com/1660-4601/13/10/1008asparaginaseacute lymphoplastic leukemiaallergyImmunogenicityproliferationapoptosiscytotoxicity |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Saleh A. Mohamed Mohamed F. Elshal Taha A. Kumosani Alia M. Aldahlawi Tasneem A. Basbrain Fauziah A. Alshehri Hani Choudhry |
spellingShingle |
Saleh A. Mohamed Mohamed F. Elshal Taha A. Kumosani Alia M. Aldahlawi Tasneem A. Basbrain Fauziah A. Alshehri Hani Choudhry L-Asparaginase Isolated from Phaseolus vulgaris Seeds Exhibited Potent Anti-Acute Lymphoblastic Leukemia Effects In-Vitro and Low Immunogenic Properties In-Vivo International Journal of Environmental Research and Public Health asparaginase acute lymphoplastic leukemia allergy Immunogenicity proliferation apoptosis cytotoxicity |
author_facet |
Saleh A. Mohamed Mohamed F. Elshal Taha A. Kumosani Alia M. Aldahlawi Tasneem A. Basbrain Fauziah A. Alshehri Hani Choudhry |
author_sort |
Saleh A. Mohamed |
title |
L-Asparaginase Isolated from Phaseolus vulgaris Seeds Exhibited Potent Anti-Acute Lymphoblastic Leukemia Effects In-Vitro and Low Immunogenic Properties In-Vivo |
title_short |
L-Asparaginase Isolated from Phaseolus vulgaris Seeds Exhibited Potent Anti-Acute Lymphoblastic Leukemia Effects In-Vitro and Low Immunogenic Properties In-Vivo |
title_full |
L-Asparaginase Isolated from Phaseolus vulgaris Seeds Exhibited Potent Anti-Acute Lymphoblastic Leukemia Effects In-Vitro and Low Immunogenic Properties In-Vivo |
title_fullStr |
L-Asparaginase Isolated from Phaseolus vulgaris Seeds Exhibited Potent Anti-Acute Lymphoblastic Leukemia Effects In-Vitro and Low Immunogenic Properties In-Vivo |
title_full_unstemmed |
L-Asparaginase Isolated from Phaseolus vulgaris Seeds Exhibited Potent Anti-Acute Lymphoblastic Leukemia Effects In-Vitro and Low Immunogenic Properties In-Vivo |
title_sort |
l-asparaginase isolated from phaseolus vulgaris seeds exhibited potent anti-acute lymphoblastic leukemia effects in-vitro and low immunogenic properties in-vivo |
publisher |
MDPI AG |
series |
International Journal of Environmental Research and Public Health |
issn |
1660-4601 |
publishDate |
2016-10-01 |
description |
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. |
topic |
asparaginase acute lymphoplastic leukemia allergy Immunogenicity proliferation apoptosis cytotoxicity |
url |
http://www.mdpi.com/1660-4601/13/10/1008 |
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