Open AccessThe human asparaginase enzyme (ASPG) inhibits growth in leukemic cells
Author(s) -
Stefania Belviso,
Rodolfo Iuliano,
Rosario Amato,
Nicola Perrotti,
Miranda Menniti
Publication year - 2017
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0178174
Subject(s) - k562 cells , cytotoxic t cell , enzyme , apoptosis , cell culture , biology , leukemia , biochemistry , recombinant dna , cytotoxicity , cancer cell , asparaginase , growth inhibition , microbiology and biotechnology , chemistry , in vitro , cancer , immunology , lymphoblastic leukemia , genetics , gene
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.