Anthracyclines such as
Adriamycin (ADR) and
daunomycin markedly inhibit cell growth in vivo and in vitro. These studies demonstrate that 30 microM
hemin, which induces
hemoglobin synthesis in human and murine
erythroleukemia cells in culture, markedly decreases the cytotoxicity of ADR in a variety of hemopoietic cell lines (K562, HEL-1, MEL-745, HL-60, and U937) and in erythroid burst-forming cells from normal human marrow.
Hemin failed to protect four of the five nonhemopoietic cell lines tested, including MCF-, breast
adenocarcinoma cells,
C-205 colon
carcinoma cells, mouse 3T3 fibroblasts, and mouse kidney VERO cells.
Hemin did protect human
neuroblastoma IMP-32 cells from ADR cytotoxicity; however, this nonhemopoietic cell line undergoes dendrite formation in response to
hemin induction. Cytofluorographic analysis of cellular ADR content and labeling studies with [3H]
daunomycin demonstrated that
hemin decreases the intracellular accumulation of these
anthracyclines by more than 50% in K562
erythroleukemia cells. These studies indicate that small doses of
hemin prevent intracellular accumulation of
anthracyclines and thereby markedly reduce
anthracycline toxicity to cells. Since this protective effect is observed preferentially with hemopoietic cells, it is possible that this finding could be exploited to protect the bone marrow from the cytotoxic action of
anthracyclines during
therapy for nonhemopoietic
tumors.