Biochemical effect of three different inhibitors of purine/pyrimidine metabolism on differentiation in HL60 cells

Leukemia Research
N Ahmed, M J Weidemann

Abstract

The effects of three different nucleotide biosynthesis inhibitors were tested on differentiation and purine/pyrimidine metabolism in HL60 cells. On the three nucleotide biosynthesis inhibitors, acivicin and mycophenolic acid were able to differentiate HL60 cells, while alanosine failed to do so. Differentiation of HL60 cells by acivicin and mycophenolic acid was associated with substantial decreases in both the guanylate and adenylate pools and appeared to be dependent on the state of depletion of intracellular GTP. Simultaneous addition of guanosine or guanine to mycophenolic acid-treated cells restored the GTP pool and prevented differentiation from occurring. Adenine or adenosine had no such effect, while hypoxanthine and inosine partially reversed the differentiation. In acivicin-treated cells, simultaneous addition of guanine caused partial prevention of differentiation. Even though treatment of HL60 cells with alanosine resulted in the depletion of guanylates, this effect was secondary to the depletion of adenylates and developed only upon prolonged exposure. In all the inhibitor-treated cells the activities of the key regulatory enzymes of de novo purine biosynthesis were affected. Even though the measurable activity of ...Continue Reading

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Citations

Apr 21, 2010·Marine Biotechnology·Sung-Ho OhHyeon-Yong Lee
Dec 6, 2012·Leukemia Research and Treatment·Geoffrey Brown, Philip Hughes
Jan 23, 2009·PloS One·Stefano TizianiUlrich L Günther
Aug 2, 2005·Journal of Biochemistry and Molecular Biology·Mohammad Amin MoosaviMohammad Hasan Sanati
Sep 8, 2004·International Journal of Cancer. Journal International Du Cancer·Elisa MessinaAlessandro Giacomello
Dec 30, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Naoko TakebeGuido Tricot
Mar 15, 2011·Toxicology and Applied Pharmacology·Azadeh MeshkiniKazem Nouri

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