Tumor Biology

, Volume 37, Issue 5, pp 6627–6635 | Cite as

Blocking autophagy enhanced leukemia cell death induced by recombinant human arginase

Original Article

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.

Keywords

Recombinant human arginase Autophagy Apoptosis Leukemia 

Notes

Acknowledgments

This work was supported by grants from the National Key Basic Research Program of China (2013CB932502, 2015CB931800), the National Natural Science Foundation of China (81573332), and Shanghai Science and Technology Funds (14431900200).

Compliance with ethical standards

Conflicts of interest

None

Supplementary material

13277_2015_4253_Fig6_ESM.jpg (19 kb)
Supplementary Figure 1

rhArg induced formation of autophagosomes in leukemia cells. HL-60 and Jurkat cells were treated with or without 1 IU/ml of rhArg for 24 h. Cell samples were prepared for transmission electron microscopy analysis as described in “Materials and methods.” Autophagosomes were counted, and the data were presented as the means ± SD of four samples. **p < 0.01 versus Ctrl; ***p < 0.001 versus Ctrl (JPEG 19 kb)

13277_2015_4253_MOESM1_ESM.tif (4.1 mb)
High resolution image (TIFF 4211 kb)

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  1. 1.Department of Biosynthesis and The Key Laboratory of Smart Drug Delivery, MOE, School of PharmacyFudan UniversityShanghaiChina
  2. 2.Department of Nephrology, Changhai HospitalSecond Military Medical UniversityShanghaiChina

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