College of Life Sciences, Cancer Hospital & Research Institute, Gwalior, MP 474009, India.
College of Life Sciences, Cancer Hospital & Research Institute, Gwalior, MP 474009, India; Department of Pharmaceutics, College of Pharmacy, PO Box 2457, King Saud University, Riyadh 11451, Saudi Arabia.
Crit Rev Oncol Hematol. 2016 Apr;100:1-10. doi: 10.1016/j.critrevonc.2015.01.002. Epub 2015 Jan 12.
L-Asparaginase (EC3.5.1.1) is an enzyme, which is used for treatment of acute lymphoblastic leukaemia (ALL) and other related blood cancers from a long time. This enzyme selectively hydrolyzes the extracellular amino acid L-asparagine into L-aspartate and ammonia, leading to nutritional deficiencies, protein synthesis inhibition, and ultimately death of lymphoblastic cells by apoptosis. Currently, bacterial asparaginases are used for treatment purpose but offers scepticism due to a number of toxicities, including thrombosis, pancreatitis, hyperglycemia, and hepatotoxicity. Resistance towards bacterial asparaginase is another major disadvantage during cancer management. This situation attracted attention of researchers towards alternative sources of L-asparaginase, including plants and fungi. Present article discusses about potential of L-asparaginase as an anticancer agent, its mechanism of action, and adverse effects related to current asparaginase formulations. This article also provides an outlook for recent developments in L-asparaginase discovery from alternative sources and their potential as a less toxic alternative to current formulations.
L-天冬酰胺酶(EC3.5.1.1)是一种酶,长期以来一直用于治疗急性淋巴细胞白血病(ALL)和其他相关血液癌。该酶选择性地将细胞外氨基酸 L-天冬酰胺水解为 L-天冬氨酸和氨,导致营养缺乏、蛋白质合成抑制,最终通过细胞凋亡导致淋巴细胞死亡。目前,细菌来源的天冬酰胺酶用于治疗目的,但由于多种毒性,包括血栓形成、胰腺炎、高血糖和肝毒性,引起了人们的质疑。对细菌来源的天冬酰胺酶的耐药性是癌症治疗中的另一个主要缺点。这种情况引起了研究人员对 L-天冬酰胺酶替代来源的关注,包括植物和真菌。本文讨论了 L-天冬酰胺酶作为抗癌剂的潜力、其作用机制以及与当前天冬酰胺酶制剂相关的不良反应。本文还展望了从替代来源发现 L-天冬酰胺酶的最新进展及其作为当前制剂毒性较小替代品的潜力。