Blocking Autophagy enhanced Leukemia Cell Death Induced by Recombinant Human Arginase

Overview

Journal Tumour Biol

Publisher Sage Publications

Specialty Oncology

Date 2015 Dec 9

PMID 26643895

Citations 12

Authors

Yubin Li

Xian Zeng

Shaofei Wang

Jiajun Fan

Ziyu Wang

Ping Song

Xiaobin Mei

Dianwen Ju

Affiliations

Soon will be listed here.

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.

Citing Articles

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6-(Methylsulfonyl) Hexyl Isothiocyanate: A Chemopreventive Agent Inducing Autophagy in Leukemia Cell Lines.

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Arginase: Mechanisms and Clinical Application in Hematologic Malignancy.

Du Z, Li T, Huang J, Chen Y, Chen C Front Oncol. 2022; 12:905893.

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Amino Acid Metabolic Vulnerabilities in Acute and Chronic Myeloid Leukemias.

Bhingarkar A, Vangapandu H, Rathod S, Hoshitsuki K, Fernandez C Front Oncol. 2021; 11:694526.

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References

Mussai F, Egan S, Higginbotham-Jones J, Perry T, Beggs A, Odintsova E . Arginine dependence of acute myeloid leukemia blast proliferation: a novel therapeutic target. Blood. 2015; 125(15):2386-96. PMC: 4416943. DOI: 10.1182/blood-2014-09-600643. View

Wan G, Xie W, Liu Z, Xu W, Lao Y, Huang N . Hypoxia-induced MIR155 is a potent autophagy inducer by targeting multiple players in the MTOR pathway. Autophagy. 2013; 10(1):70-9. PMC: 4389881. DOI: 10.4161/auto.26534. View

Vogel R, Coughlin K, Scotti A, Iizuka Y, Anchoori R, Roden R . Simultaneous inhibition of deubiquitinating enzymes (DUBs) and autophagy synergistically kills breast cancer cells. Oncotarget. 2015; 6(6):4159-70. PMC: 4414179. DOI: 10.18632/oncotarget.2904. View

Qiu F, Chen Y, Liu X, Chu C, Shen L, Xu J . Arginine starvation impairs mitochondrial respiratory function in ASS1-deficient breast cancer cells. Sci Signal. 2014; 7(319):ra31. PMC: 4229039. DOI: 10.1126/scisignal.2004761. View

Young C, Sinadinos A, Lefebvre A, Chan P, Arkle S, Vaudry D . A novel mechanism of autophagic cell death in dystrophic muscle regulated by P2RX7 receptor large-pore formation and HSP90. Autophagy. 2015; 11(1):113-30. PMC: 4502824. DOI: 10.4161/15548627.2014.994402. View

Tiwana G, Prevo R, Buffa F, Yu S, Ebner D, Howarth A . Identification of vitamin B1 metabolism as a tumor-specific radiosensitizing pathway using a high-throughput colony formation screen. Oncotarget. 2015; 6(8):5978-89. PMC: 4467415. DOI: 10.18632/oncotarget.3468. View

Chow A, Ng L, Li H, Cheng C, Lam C, Yau T . Anti-tumor efficacy of a recombinant human arginase in human hepatocellular carcinoma. Curr Cancer Drug Targets. 2012; 12(9):1233-43. DOI: 10.2174/156800912803988002. View

Bassan R, Masciulli A, Intermesoli T, Audisio E, Rossi G, Pogliani E . Randomized trial of radiation-free central nervous system prophylaxis comparing intrathecal triple therapy with liposomal cytarabine in acute lymphoblastic leukemia. Haematologica. 2015; 100(6):786-93. PMC: 4450624. DOI: 10.3324/haematol.2014.123273. View

Gervasini G, Vagace J . Impact of genetic polymorphisms on chemotherapy toxicity in childhood acute lymphoblastic leukemia. Front Genet. 2012; 3:249. PMC: 3504364. DOI: 10.3389/fgene.2012.00249. View

10.

Wang S, Li Y, Fan J, Wang Z, Zeng X, Sun Y . The role of autophagy in the neurotoxicity of cationic PAMAM dendrimers. Biomaterials. 2014; 35(26):7588-97. DOI: 10.1016/j.biomaterials.2014.05.029. View

11.

Shi X, Li Y, Fan J, Zeng X, Xian Z, Wang Z . Blocking autophagy enhanced cytotoxicity induced by recombinant human arginase in triple-negative breast cancer cells. Cell Death Dis. 2014; 5:e1563. PMC: 4454157. DOI: 10.1038/cddis.2014.503. View

12.

Li Y, Zeng X, Wang S, Sun Y, Wang Z, Fan J . Inhibition of autophagy protects against PAMAM dendrimers-induced hepatotoxicity. Nanotoxicology. 2014; 9(3):344-55. DOI: 10.3109/17435390.2014.930533. View

13.

Zhang J, Fan J, Venneti S, Cross J, Takagi T, Bhinder B . Asparagine plays a critical role in regulating cellular adaptation to glutamine depletion. Mol Cell. 2014; 56(2):205-218. PMC: 4224619. DOI: 10.1016/j.molcel.2014.08.018. View

14.

Zeng X, Zhao H, Li Y, Fan J, Sun Y, Wang S . Targeting Hedgehog signaling pathway and autophagy overcomes drug resistance of BCR-ABL-positive chronic myeloid leukemia. Autophagy. 2015; 11(2):355-72. PMC: 4502679. DOI: 10.4161/15548627.2014.994368. View

15.

Ma D, Fang Q, Wang P, Gao R, Wu W, Lu T . Induction of heme oxygenase-1 by Na+-H+ exchanger 1 protein plays a crucial role in imatinib-resistant chronic myeloid leukemia cells. J Biol Chem. 2015; 290(20):12558-71. PMC: 4432277. DOI: 10.1074/jbc.M114.626960. View

16.

Song P, Ye L, Fan J, Li Y, Zeng X, Wang Z . Asparaginase induces apoptosis and cytoprotective autophagy in chronic myeloid leukemia cells. Oncotarget. 2015; 6(6):3861-73. PMC: 4414159. DOI: 10.18632/oncotarget.2869. View

17.

Christiansson L, Soderlund S, Mangsbo S, Hjorth-Hansen H, Hoglund M, Markevarn B . The tyrosine kinase inhibitors imatinib and dasatinib reduce myeloid suppressor cells and release effector lymphocyte responses. Mol Cancer Ther. 2015; 14(5):1181-91. DOI: 10.1158/1535-7163.MCT-14-0849. View

18.

Hori Y, Hosoda R, Akiyama Y, Sebori R, Wanibuchi M, Mikami T . Chloroquine potentiates temozolomide cytotoxicity by inhibiting mitochondrial autophagy in glioma cells. J Neurooncol. 2014; 122(1):11-20. DOI: 10.1007/s11060-014-1686-9. View

19.

Queiroz E, Puukila S, Eichler R, Sampaio S, Forsyth H, Lees S . Metformin induces apoptosis and cell cycle arrest mediated by oxidative stress, AMPK and FOXO3a in MCF-7 breast cancer cells. PLoS One. 2014; 9(5):e98207. PMC: 4032293. DOI: 10.1371/journal.pone.0098207. View

20.

Dillon B, Prieto V, Curley S, Ensor C, Holtsberg F, Bomalaski J . Incidence and distribution of argininosuccinate synthetase deficiency in human cancers: a method for identifying cancers sensitive to arginine deprivation. Cancer. 2004; 100(4):826-33. DOI: 10.1002/cncr.20057. View