title: Human recombinant arginase I(Co)-PEG5000 [HuArgI(Co)-PEG5000]-induced arginine depletion is selectively cytotoxic to human acute myeloid leukemia cells.
abstract: In this study, we target arginine auxotrophy of AML cell lines using human arginase I cobalt-PEG5000. HuArgI(Co)-PEG5000 was cytotoxic to all AML cell lines tested. Mononuclear cells and CD34(+) blasts were not sensitive demonstrating the selectivity of HuArgI(Co)-PEG5000-induced arginine deprivation. Addition of L-citrulline led to the rescue of five cell lines. The four cell lines that were not rescued by L-citrulline did not express argininosuccinate synthetase-1, indicating complete arginine auxotrophy. Inhibition of autophagy increased cell sensitivity to HuArgI(Co)-PEG5000 demonstrating the protective role of autophagy following arginine deprivation. We have shown that AML can be selectively targeted using HuArgI(Co)-PEG5000-induced arginine depletion.
authors.affiliation: Department of Natural Sciences, School of Arts and Sciences, Lebanese American University, Beirut 1102 2801, Lebanon.
authors.forename: Rita
authors.initials: R
authors.lastname: Tanios
authors.forename: Amira
authors.initials: A
authors.lastname: Bekdash
authors.forename: Elias
authors.initials: E
authors.lastname: Kassab
authors.forename: Everett
authors.initials: E
authors.lastname: Stone
authors.forename: Georges
authors.initials: G
authors.lastname: Georgiou
authors.forename: Arthur E
authors.initials: AE
authors.lastname: Frankel
authors.forename: Ralph J
authors.initials: RJ
authors.lastname: Abi-Habib
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001119:Arginase / Q000378:metabolism*; D001120:Arginine / Q000378:metabolism*; D001124:Argininosuccinate Synthase; D001343:Autophagy; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011994:Recombinant Proteins / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D001120:Arginine; C574619:ARG1 protein, human; D001119:Arginase; D001124:Argininosuccinate Synthase
keywords: AML; Arginine; Autophagy; HuArgI(Co)-PEG5000