title: Blocking autophagy enhanced cytotoxicity induced by recombinant human arginase in triple-negative breast cancer cells.
abstract: Depletion of arginine by recombinant human arginase (rhArg) has proven to be an effective cancer therapeutic approach for a variety of malignant tumors. Triple-negative breast cancers (TNBCs) lack of specific therapeutic targets, resulting in poor prognosis and limited therapeutic efficacy. To explore new therapeutic approaches for TNBC we studied the cytotoxicity of rhArg in five TNBC cells. We found that rhArg could inhibit cell growth in these five TNBC cells. Intriguingly, accumulation of autophagosomes and autophagic flux was observed in rhArg-treated MDA-MB-231 cells. Inhibition of autophagy by chloroquine (CQ), 3-methyladenine (3-MA) and siRNA targeting Beclin1 significantly enhanced rhArg-induced cytotoxic effect, indicating the cytoprotective role of autophagy in rhArg-induced cell death. In addition, N-acetyl-l-cysteine (NAC), a common antioxidant, blocked autophagy induced by rhArg, suggesting that reactive oxygen species (ROS) had an essential role in the cytotoxicity of rhArg. This study provides new insights into the molecular mechanism of autophagy involved in rhArg-induced cytotoxicity in TNBC cells. Meanwhile, our results revealed that rhArg, either alone or in combination with autophagic inhibitors, might be a potential novel therapy for the treatment of TNBC.Cell Death and Disease (2014) 5, e1563; doi:10.1038/cddis.2014.503; published online 11 December 2014.
authors.affiliation: 1] Department of Biosynthesis and Key Lab of Smart Drug Delivery of MOE, School of Pharmacy, Fudan University, Shanghai, China [2] Department of Biopharmaceutical Research, Shanghai Institute of Pharmaceutical Industry, Shanghai, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Biosynthesis and Key Lab of Smart Drug Delivery of MOE, School of Pharmacy, Fudan University, Shanghai, China.
authors.forename: X
authors.initials: X
authors.lastname: Shi
authors.affiliation: Department of Biosynthesis and Key Lab of Smart Drug Delivery of MOE, School of Pharmacy, Fudan University, Shanghai, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Biosynthesis and Key Lab of Smart Drug Delivery of MOE, School of Pharmacy, Fudan University, Shanghai, China.
authors.forename: J
authors.initials: J
authors.lastname: Fan
authors.affiliation: Department of Biosynthesis and Key Lab of Smart Drug Delivery of MOE, School of Pharmacy, Fudan University, Shanghai, China.
authors.forename: X
authors.initials: X
authors.lastname: Zeng
authors.affiliation: Department of Biosynthesis and Key Lab of Smart Drug Delivery of MOE, School of Pharmacy, Fudan University, Shanghai, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Xian
authors.affiliation: Department of Pulmonary Medicine, People's Affiliated Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Biosynthesis and Key Lab of Smart Drug Delivery of MOE, School of Pharmacy, Fudan University, Shanghai, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Biosynthesis and Key Lab of Smart Drug Delivery of MOE, School of Pharmacy, Fudan University, Shanghai, China.
authors.forename: S
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Biosynthesis and Key Lab of Smart Drug Delivery of MOE, School of Pharmacy, Fudan University, Shanghai, China.
authors.forename: P
authors.initials: P
authors.lastname: Song
authors.affiliation: Department of Head and Neck Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: S
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Biopharmaceutical Research, Shanghai Institute of Pharmaceutical Industry, Shanghai, China.
authors.forename: H
authors.initials: H
authors.lastname: Hu
authors.affiliation: Department of Biosynthesis and Key Lab of Smart Drug Delivery of MOE, School of Pharmacy, Fudan University, Shanghai, China.
authors.forename: D
authors.initials: D
authors.lastname: Ju
mesh_terms: D017209:Apoptosis; D001119:Arginase / Q000235:genetics / Q000378:metabolism*; D001120:Arginine / Q000378:metabolism; D001343:Autophagy; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006801:Humans; D064726:Triple Negative Breast Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D001120:Arginine; D001119:Arginase