Effects of differentiation-inducing agents on purine nucleotide metabolism in an ovarian cancer cell line

Esther Zoref-Shani, Ronit Lavie, Yael Bromberg, Einat Beery, Yechezkel Sidi, Oded Sperling*, Jardena Nordenberg

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


The effects of the differentiation-inducing agents sodium butyrate (NaOBt), dimethylsulfoxide (DMSO) and mycophenolic acid (MA), on purine nucleotide metabolism, was studied in an ovarian carcinoma cell line (GZL-8). Exposure to these agents inhibited cell proliferation, but did not affect cell viability. Three hours following exposure, NaOBt and DMSO moderately decelerated purine synthesis de novo, but MA accelerated it three-fold, this being associated with a two-fold increase in the excretion of hypoxanthine and xanthine into the incubation medium. NaOBt and DMSO did not affect the cellular nucleotide content, but MA caused a 73% decrease in GTP content and about a 50% increase in the cellular content of UTP. The following alterations in cellular enzyme activity were observed 72 h following exposure: NaOBt decreased the activity of hypoxanthine-guanine phosphoribosyltransferase and increased the activity of IMP and of IMP 5′-nucleotidases, DMSO increased the activity of IMP 5′-nucleotidase, and MA increased the activity of the two nucleotidases. The results suggest that, in the carcinoma cell line studied, the differentiation process induced by NaOBt and DMSO may be associated with a general shift in the direction of purine metabolism from anabolism to catabolism, whereas that induced by MA is associated with a specific decrease in the production of GTP.

Original languageEnglish
Pages (from-to)717-722
Number of pages6
JournalJournal of Cancer Research and Clinical Oncology
Issue number12
StatePublished - Dec 1994


  • De novo purine synthesis
  • Differentiation-inducing agents
  • Dimethylsulfoxide
  • Guanine nucleotides
  • IMP dehydrogenase
  • Mycophenolic acid
  • Purine metabolism
  • Sodium butyrate


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