Blocking autophagy enhanced leukemia cell death induced by recombinant human arginase.
Recombinant human arginase (rhArg) is an arginine-degrading enzyme that has been evaluated as effective therapeutics for varieties of malignant tumors and is in clinical trials for hepatocellular carcinoma (HCC) treatment nowadays. Our previous studies have reported that rhArg could induce autophagy and apoptosis in lymphoma cells and inhibiting autophagy could enhance the efficacy of rhArg on lymphoma. However, whether rhArg could induce autophagy and what roles autophagy plays in leukemia cells are unclear. In this study, we demonstrated that rhArg treatment could lead to the formation of autophagosomes and the upregulation of microtubule-associated protein light chain 3 II (LC3-II) in human promyelocytic leukemia HL-60 cells and human acute T cell leukemia Jurkat cells. Furthermore, inhibiting autophagy using 3-methyladenine (3-MA) or chloroquine (CQ) could significantly enhance rhArg-induced cell growth inhibition and apoptosis. Taken together, these findings indicated that rhArg induced autophagy in leukemia cells and inhibiting autophagy enhanced anti-leukemia effect of rhArg, which might encourage the treatment of leukemia by targeting arginine depletion and autophagy in clinics.
['Li|Yubin|Y|', 'Zeng|Xian|X|', 'Wang|Shaofei|S|', 'Fan|Jiajun|J|', 'Wang|Ziyu|Z|', 'Song|Ping|P|', 'Mei|Xiaobin|X|', 'Ju|Dianwen|D|']
D000970:Antineoplastic Agents D017209:Apoptosis D001119:Arginase D001343:Autophagy D002453:Cell Cycle D045744:Cell Line, Tumor D049109:Cell Proliferation D018922:HL-60 Cells D006801:Humans D019169:Jurkat Cells D007938:Leukemia D011994:Recombinant Proteins
Autophagy Leukemia Recombinant human arginase Apoptosis