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Pharmacy World and Science

, Volume 16, Issue 2, pp 77–83 | Cite as

Role of differentiation induction in action of purine antimetabolites

  • George Weber
  • Yuki Hata
  • Noemi Prajda
Purine and Pyrimidine Metabolism

Abstract

In cancer cells, particularly in leukaemic cells, guanylate biosynthesis is up-regulated as shown by the increased activities of IMP dehydrogenase, the rate-limiting enzyme ofde novo GTP biosynthesis, and of the salvage enzyme, hypoxanthine-guanine phosphoribosyltransferase (HGPRT). In enzyme pattern-targeted chemotherapy, tiazofurin inhibits IMP dehydrogenase activity in cancer cells and allopurinol-induced high serum hypoxanthine levels inhibit. HGPRT activity. A triad of responses was observed in the blast cells of patients treated with tiazofurin infusions: chemotherapy, induced differentiation, and down-regulation of c-Ki-ras andc-myc oncogenes. Tiazofurin was synergistic in cytotoxicity and in causing differentiation with ribavirin, retinoic acid, and difluorodeoxycytidine. Induced differentiation plays an important role in the overall impact of antipurine agents.

Keywords

Differentiation Drug synergism Gemcitabine Hypoxanthine-guanine phosphoribosyltransferase IMP dehydrogenase Leukemia, myeloid, chronic Oncogenes Ribavirin Tiazofurin 

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Copyright information

© Royal Dutch Association for the Advancement of Pharmacy 1994

Authors and Affiliations

  • George Weber
    • 1
  • Yuki Hata
    • 1
  • Noemi Prajda
    • 1
  1. 1.Laboratory for Experimental OncologyIndiana University School of MedicineIndianapolisUSA

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