Mohamed Saleh A, Elshal Mohamed F, Kumosani Taha A, Aldahlawi Alia M, Basbrain Tasneem A, Alshehri Fauziah A, Choudhry Hani
Biochemistry Department, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
Biology Department, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
Int J Environ Res Public Health. 2016 Oct 14;13(10):1008. doi: 10.3390/ijerph13101008.
-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 -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 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 (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.
源自[具体来源未提及]的L-天冬酰胺酶已被用于治疗急性淋巴细胞白血病(ALL),然而,临床过敏反应以及由于针对天冬酰胺酶的抗体导致的沉默失活,在大多数情况下会使这些制剂失活。因此,本研究旨在调查从[种子名称未提及]种子中分离出的一种新型L-天冬酰胺酶(P-Asp)对ALL细胞系(Jurkat)的细胞毒性和抗肿瘤作用。还在体内评估了该酶的免疫原性,并将结果与市售微生物来源的酶进行了比较。数据表明,通过WST-8细胞活力检测试剂盒检测,P-Asp对ALL细胞具有增强的抗增殖作用。与来自[具体来源未提及]的天冬酰胺酶(L-Asp)或其聚乙二醇化形式培门冬酶(PEG-ASP)相比,用P-Asp处理的细胞也表现出更高程度的早期凋亡,通过膜联蛋白V/碘化丙啶结合检测发现,L-Asp或PEG-ASP诱导更高的晚期凋亡和坏死率。体内实验表明,与其他治疗组相比,用P-Asp处理的小鼠血清中IgG、IgE、IgM和mMCP-1的浓度较低,表明其过敏反应比其他细菌酶制剂更不明显。总之,P-Asp可被视为治疗ALL的有前途的候选药物。