Department of Biotechnology, Rabe Rashid Institute, Tabriz, Iran; Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Cancer and Inflammation Research, Institute for Molecular Medicine, University of Southern Denmark, Odense, Denmark.
Int J Biol Macromol. 2021 Feb 15;170:406-414. doi: 10.1016/j.ijbiomac.2020.12.141. Epub 2020 Dec 30.
L-asparaginase is an enzyme capable of hydrolyzing the asparagine to aspartic acid and ammonia. L-asparaginase is widely used in the treatment of acute lymphoblastic leukemia (ALL) and other cancers. Here, for the first time, the effects of a novel yeast L-asparaginase from Yarrowia lipolytica were studied on human lung (A549) and breast cancer (MCF7) cell lines as the solid cancer cell lines in terms of cell growth and metastasis inhibition. Functional analysis showed the L-asparagine deprivation mediated anti-proliferation effects by apoptosis induction and changes in the expression of target genes involved in apoptosis and migration pathways. The qRT-PCR analysis showed the higher expression levels of pro-apoptosis genes, including Bax, P53, caspase 3, caspase 8, and down-regulation of Bcl-2 anti-apoptotic gene in treated cells. On the other hand, there was no increase in ROS production in the treated cells. However, L-asparaginase treatment was able to significantly induce autophagy activation in A549 cells. Besides, wound healing assay showed that L-asparaginase could considerably inhibit the migration of A549 and MCF7 cells. Taken together, our results suggested that Yarrowia lipolytica L-asparaginase might be considered for enzyme therapy against breast and lung cancers.
天冬酰胺酶是一种能够将天冬酰胺水解为天冬氨酸和氨的酶。天冬酰胺酶被广泛用于治疗急性淋巴细胞白血病（ALL）和其他癌症。在这里，首次研究了来自解脂耶氏酵母的新型酵母天冬酰胺酶对人肺癌（A549）和乳腺癌（MCF7）细胞系作为实体癌细胞系的抑制细胞生长和转移的作用。功能分析表明，天冬酰胺剥夺通过诱导细胞凋亡和改变细胞凋亡和迁移途径相关靶基因的表达来发挥抗增殖作用。qRT-PCR 分析显示，在处理过的细胞中，促凋亡基因，包括 Bax、P53、caspase 3、caspase 8 的表达水平升高，而抗凋亡基因 Bcl-2 的表达下调。另一方面，处理过的细胞中 ROS 的产生并没有增加。然而，天冬酰胺酶处理能够显著诱导 A549 细胞中的自噬激活。此外，划痕愈合试验表明，天冬酰胺酶能够显著抑制 A549 和 MCF7 细胞的迁移。综上所述，我们的研究结果表明，解脂耶氏酵母天冬酰胺酶可能被考虑用于治疗乳腺癌和肺癌的酶疗法。
