Synergistic cytotoxicity of AZT plus alpha and gamma interferon in chronic myeloid leukemia cell line K562

P. Tosi, G. Visani, E. Ottaviani, B. Gamberi, A. Cenacchi, S. Tura

Research output: Contribution to journalArticlepeer-review

Abstract

We have previously reported that the antineoplastic activity of 3'-azido 3' deoxythymidine (AZT) can be increased by drugs that inhibit 'de novo' thymidylate synthesis, such as 5-fluorouracil, methotrexate and hydroxyurea. In the present study we tested the combinations AZT + alpha interferon (IFN) and AZT + gamma IFN on in vitro growth of the human acute-phase chronic myeloid leukemia (CML) cell line K562. After 72 hours incubation, not only AZT + α-IFN but also AZT + γ-IFN were synergistic in inhibiting K562 growth, as demonstrated by isobologram analysis of the data. This enhanced cytotoxicity was confirmed by the evaluation of [3H]AZT incorporation into cellular DNA, that was increased by 50% and 222% in the presence of α- and γ-IFN, respectively. The addition of 50 μmol/l thymidine to the culture medium was able to reduce the cytotoxicity of the drug combinations to the degree observed with each compound alone; furthermore, the increased incorporation of AZT into DNA was completely reversed. These data indicate the existence of a biochemical interaction between AZT and IFNs that results in an increased cytotoxic effect. While the combination AZT + α-IFN is currently being tested in HIV-related malignancies, AZT + γ-IFN is new and deserves further study in human CML acute and chronic phase models, in view of possible clinical applications.

Original languageEnglish
Pages (from-to)209-213
Number of pages5
JournalEuropean Journal of Haematology
Volume51
Issue number4
Publication statusPublished - 1993

ASJC Scopus subject areas

  • Hematology

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