The potentiated antileukemic effects of doxorubicin and interleukin-12 combination are not dependent on nitric oxide production

Citation
R. Zagozdzon et al., The potentiated antileukemic effects of doxorubicin and interleukin-12 combination are not dependent on nitric oxide production, CANCER LETT, 147(1-2), 1999, pp. 67-75
Citations number
27
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
CANCER LETTERS
ISSN journal
03043835 → ACNP
Volume
147
Issue
1-2
Year of publication
1999
Pages
67 - 75
Database
ISI
SICI code
0304-3835(199912)147:1-2<67:TPAEOD>2.0.ZU;2-S
Abstract
In our recent study we described a significant antileukemic efficacy of a c ombination therapy with interleukin-12 (IL-12) and doxorubicin (DOX) in the L1210 leukemia model. This therapeutic effect was abrogated by elimination of activated macrophages. Activated macrophages produce a variety of facto rs that can contribute to the elimination of tumor cells in vivo, including proteases, TNF, reactive oxygen intermediates, and nitric oxide (NO). Base d on the results of previous reports, the contribution of NO in potentiated antileukemic effects of IL-12 + DOX combination seemed to be highly possib le. Both DOX and IL-12 given alone increased the production of NO by perito neal macrophages, however, macrophages derived from the mice treated with t he combination of those agents produced significantly less NO than macropha ges from IL-12-alone-treated mice. Production of NO by spleen macrophages a fter IL-12 + DOX treatment was higher than it was in controls, IL-12-alone- or DOX-alone-treated groups. In serum, concentrations of NOx- in IL-12- or IL-12 + DOX-treated mice were significantly higher in comparison with contr ols, however not significantly different from each other. Addition of L-NAM E treatment to the IL-12 + DOX therapy in leukemia-bearing mice did not sig nificantly change the antileukemic efficacy of this therapy. Thus, our resu lts indicate that the augmented antileukemic effects of IL-12 + DOX combina tion therapy in L1210 model are NO-independent. Therefore, further studies on the possible mechanisms of potentiated antileukemic activity of combinat ion of IL-12 and DOX would be worth pursuing. (C) 1999 Elsevier Science Ire land Ltd. All rights reserved.