Nuclear microprobe analysis of iodine and iron distributions in tumor cells exposed to the anthracycline 4'-iodo-4'- deoxydoxorubicin

In this study, we performed nuclear microprobe analysis on cultured human ovarian cancer cells exposed to pharmacological concentrations of 4′-iodo-4′-deoxydoxorubicin (IDX), an anthracycline anticancer drug. We observed that iodine and iron cellular distributions were strongly correlated, suggesting intracellular iron chelation by the anthracycline. The average cellular iron concentration did not change during drug exposure, but the cellular distribution of iron was modified following the preferential nuclear localization of iodine, as determined by single cell microanalysis. These results are important for understanding the cellular pharmacology of anthracyclines. They suggest that iron cellular delocalization and its subsequent nuclear accumulation may participate to the overall cytotoxicity of IDX, and more generally to anthracycline antitumor activity.