Aspects of the cellular pharmacology of N-l-leucyldoxorubicin in human tumor cell lines.

We have compared the cytotoxicity, incorporation and metabolism of doxorubicin (dox) and N-l-leucyldoxorubicin (leu-dox) in two human tumor cell lines in culture, the MCF-7 breast cancer line and the K562 leukemia line, and their dox-resistant counterparts. Dox was 3-4-fold more cytotoxic than leu-dox in the MCF-7 lines, and 7-10-fold in the K562 lines. This could be explained by differences in cell incorporation of the drugs, which differs by the same proportion as the cytotoxicities in the various cell lines, rather than by differences in biotransformation of leu-dox into dox, which is similar in all of the cell lines.