Influence of ICRF-159 or ICRF-186 on cytotoxicity of daunorubicin and doxorubicin.

It has been shown that ICRF-159 [1,2-bis(3,5-dioxopiperazine-1-yl)propane] and its more water soluble d-enantiomer, ICRF-186, antagonize the toxicity of daunorubicin and the cardiac toxicity of daunorubicin and doxorubicin and potentiate the antitumor effect of both substances in experimental animals. In particular, the antagonism against general toxicity was observed in combination with daunorubicin but not with doxorubicin. In this study, we evaluated the activity of ICRF-159 and ICRF-186 on the colony inhibition test of HeLa cells in vitro in combination with daunorubicin or doxorubicin. ICRF-159 and ICRF-186 similarly antagonize the cytotoxicity of daunorubicin but not of doxorubicin. There were no differences between ICRF-159 and ICRF-186, dissolved in DMSO and in physiological solution, respectively. The different activity of ICRF-159 and ICRF-186 against daunorubicin and doxorubicin is not explained by a different uptake of the anthracyclines by HeLa cells in vitro. In the present paper we report findings from our in vitro colony forming assay with HeLa cells, which has been used to evaluate the cytotoxicity of ICRF-159 and ICRF-186 in the presence of daunorubicin and doxorubicin.