The human asparaginase enzyme (ASPG) inhibits growth in leukemic cells

• Published in: PloS one 2017-05, Vol.12 (5), p.e0178174-e0178174
• Main Authors: Belviso, Stefania, Iuliano, Rodolfo, Amato, Rosario, Perrotti, Nicola, Menniti, Miranda
• Format: Article
• Language: English
• Subjects: 1-Alkyl-2-acetylglycerophosphocholine esterase; 1-Alkyl-2-acetylglycerophosphocholine Esterase - genetics; 1-Alkyl-2-acetylglycerophosphocholine Esterase - therapeutic use; Absorbance; Acetylcholinesterase; Acute lymphoblastic leukemia; Adhesives; Affinity; Affinity chromatography; Amiloride; Amino Acid Substitution; Amino acids; Ammonia; Ammonium; Ammonium sulfate; Ampicillin; Amplification; Angiogenesis; Ankyrins; Anticancer properties; Antineoplastic Agents - therapeutic use; Apolipoprotein E; Apoptosis; Apoptosis - drug effects; Asparaginase; Asparaginase - genetics; Asparaginase - therapeutic use; Autophagy; Bacteria; Biocompatibility; Biology and Life Sciences; Biotechnology; Breast cancer; Cancer; Cancer cells; Catalysis; Cell cycle; Cell growth; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Clinical medicine; Cloning; Cytotoxicity; Deamination; Deoxyribonucleic acid; DNA; Engineering; Enzymatic activity; Enzymes; Epithelial Sodium Channels - metabolism; Ethylenediaminetetraacetic acids; Fragmentation; Health care; Humans; Immunology; Inhibition; Inhibitors; K562 Cells; Kinases; Leukemia; Leukemia - drug therapy; Leukemia - metabolism; Leukemia - pathology; Lymphatic leukemia; Lysis; Medicine and Health Sciences; Metabolism; Mice; Microbiology; Mutagenesis, Site-Directed; Mutants; Myeloid leukemia; Oligonucleotides; Oxidative stress; Phosphates; Physical Sciences; Proteins; Purification; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - therapeutic use; Research and Analysis Methods; Rodents; Side effects; Structural analysis; Toxicity; Tumor suppressor genes; Tumorigenesis; Tumors; Viability
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0178174

The human protein ASPG is an enzyme with a putative antitumor activity. We generated in bacteria and then purified a recombinant GST-ASPG protein that we used to characterize the biochemical and cytotoxic properties of the human ASPG. We demonstrated that ASPG possesses asparaginase and PAF acetylhydrolase activities that depend on a critical threonine residue at position 19. Consistently, ASPG but not its T19A mutant showed cytotoxic activity in K562, NALM-6 and MOLT-4 leukemic cell lines but not in normal cells. Regarding the mechanism of action of ASPG, it was able to induce a significant apoptotic death in K562 cells. Taken together our data suggest that ASPG, combining different enzymatic activities, should be considered a promising anti-cancer agent for inhibiting the growth of leukemia cells.