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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
Author(s) -
Forsbeck Klas,
Nilsson Kenneth,
Kontoghiorghes George J.
Publication year - 1987
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/j.1600-0609.1987.tb00776.x
Subject(s) - chemistry , transferrin , pyridoxal , cytotoxic t cell , deferiprone , chelation , biochemistry , tropolone , maltol , stereochemistry , in vitro , enzyme , deferoxamine , organic chemistry
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‐hydroxyquinoline 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.