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 journalArticle

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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

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Myeloid Cells
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Interferon-alpha
Interferons
Interferon-gamma
Cell Line
Leukemia, Myeloid, Chronic Phase
Hydroxyurea
Zidovudine
DNA
Drug Combinations
Growth
Methotrexate
Fluorouracil
Antineoplastic Agents
Thymidine
Culture Media
HIV
Pharmaceutical Preparations
Neoplasms

ASJC Scopus subject areas

  • Hematology

Cite this

Synergistic cytotoxicity of AZT plus alpha and gamma interferon in chronic myeloid leukemia cell line K562. / Tosi, P.; Visani, G.; Ottaviani, E.; Gamberi, B.; Cenacchi, A.; Tura, S.

In: European Journal of Haematology, Vol. 51, No. 4, 1993, p. 209-213.

Research output: Contribution to journalArticle

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AU - Tosi, P.

AU - Visani, G.

AU - Ottaviani, E.

AU - Gamberi, B.

AU - Cenacchi, A.

AU - Tura, S.

PY - 1993

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