1. The human asparaginase enzyme (ASPG) inhibits growth in leukemic cells.
- Author
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Belviso S, Iuliano R, Amato R, Perrotti N, and Menniti M
- Subjects
- 1-Alkyl-2-acetylglycerophosphocholine Esterase genetics, 1-Alkyl-2-acetylglycerophosphocholine Esterase therapeutic use, Amino Acid Substitution, Apoptosis drug effects, Asparaginase genetics, Cell Line, Tumor, Cell Proliferation drug effects, Cell Survival drug effects, Epithelial Sodium Channels metabolism, Humans, K562 Cells, Leukemia metabolism, Leukemia pathology, Mutagenesis, Site-Directed, Recombinant Fusion Proteins genetics, Recombinant Fusion Proteins therapeutic use, Antineoplastic Agents therapeutic use, Asparaginase therapeutic use, Leukemia drug therapy
- Abstract
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.
- Published
- 2017
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