title: Blocking autophagy enhanced leukemia cell death induced by recombinant human arginase.
abstract: 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.
authors.affiliation: Department of Biosynthesis and The Key Laboratory of Smart Drug Delivery, MOE, School of Pharmacy, Fudan University, Shanghai, 201203, China.
authors.forename: Yubin
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Biosynthesis and The Key Laboratory of Smart Drug Delivery, MOE, School of Pharmacy, Fudan University, Shanghai, 201203, China.
authors.forename: Xian
authors.initials: X
authors.lastname: Zeng
authors.affiliation: Department of Biosynthesis and The Key Laboratory of Smart Drug Delivery, MOE, School of Pharmacy, Fudan University, Shanghai, 201203, China.
authors.forename: Shaofei
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Biosynthesis and The Key Laboratory of Smart Drug Delivery, MOE, School of Pharmacy, Fudan University, Shanghai, 201203, China.
authors.forename: Jiajun
authors.initials: J
authors.lastname: Fan
authors.affiliation: Department of Biosynthesis and The Key Laboratory of Smart Drug Delivery, MOE, School of Pharmacy, Fudan University, Shanghai, 201203, China.
authors.forename: Ziyu
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Biosynthesis and The Key Laboratory of Smart Drug Delivery, MOE, School of Pharmacy, Fudan University, Shanghai, 201203, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Song
authors.affiliation: Department of Nephrology, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China. meixiaobin@medmail.com.cn.
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Mei
authors.affiliation: Department of Biosynthesis and The Key Laboratory of Smart Drug Delivery, MOE, School of Pharmacy, Fudan University, Shanghai, 201203, China. dianwenju@fudan.edu.cn.
authors.forename: Dianwen
authors.initials: D
authors.lastname: Ju
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001119:Arginase / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D019169:Jurkat Cells; D007938:Leukemia / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D011994:Recombinant Proteins; D001119:Arginase
keywords: Apoptosis; Autophagy; Leukemia; Recombinant human arginase