Variation in iron accumulation, transferrin membrane binding and DNA synthesis in the K‐562 and U‐937 cell lines induced by chelators and their iron complexes

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Abstract
Eight chelators - 8-hydroxyquinoline, 1-hydroxypyridine-2-thione (omadine), tropolone, pyridoxal isonicotinoyl hydrazone, 2-methyl-3-hydroxypyr-4-one (maltol), 1-methyl-3-hydroxypyrid-2-one, 1,2-dimethyl-3-hydroxypyrid-4-one and mimosine - and their iron complexes were tested on cells of the established human tumour cell lines K-562 (erythroleukaemic) and U-937 (monoblastoid) for their effects on a) cellular accumulation of iron provided by transferrin (Tf) via receptor-mediated endocytosis, b) specific cell surface binding of Tf, c) cell viability and, d) DNA synthesis. The lipophilic chelators suppressed the accumulation of Tf-supplied iron in the K-562 cells and less so in the U-937 cells, whereas the effects of the other chelators were closer to control range. The lipophilic chelators pyridoxal isonicotinoyl hydrazone, tropolone, 8-hydroxyquinoline and omadine were found to be cytotoxic in this order, with the U-937 being generally more sensitive than K-562. The presence of iron diminished the toxicity. The DNA synthesis was also affected, from a partial suppression in K-562 to a slight increase in U-937 in the presence of pyridoxal isonicotinoyl hydrazone and to strong suppression with 8-hydroxyguinoline and omadine. Addition of iron partially reversed the inhibition. The other chelators had low cytotoxic effects that disappeared upon iron saturation. Maltol, particularly in the absence of iron, 1,2-dimethyl-3-hydroxypyrid-4-one and 1-methyl-3-hydroxypyrid-2-one supported DNA synthesis. Long-term culturing (24 h) of both cell types in the presence of the non-cytotoxic chelators resulted in increased specific Tf binding, which was interpreted as the result of an increased Tf-receptor synthesis. This is presumably triggered via the chelators'' interaction with a certain cellular iron pool.