Role of iron in the proliferation of the established human tumor cell lines U-937 and K-562: effects of suramin and a lipophilic iron chelator (PIH).
Suramin was used to analyze the growth-effects of blockade of iron uptake on two established human cell lines, U-937 (monocytoid) and K-562 (erythroleukemic). Suramin suppressed cell surface transferrin (Tf) binding and uptake of iron via inhibition of receptor-mediated endocytosis (RME). As a result, both lines accumulated in the S-phase. DNA synthesis and cell division were inhibited in the suramin-treated U-937, but not in K-562. Iron, supplied by a route alternative to Tf-to suramin-suppressed U-937 cells, reinitiated DNA synthesis and cell division, although at a lower level than in control cells. Multiple effects on iron-dependent enzymes and an inhibition of binding of undefined growth factors necessary for the transition through the cell cycle are suggested to be mechanisms by which suramin affects the U-937 cells. The results imply that clinically observed side effects of suramin may be caused by interference with cellular iron metabolism.
D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004247:DNA / Q000096:biosynthesis; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D007501:Iron / Q000378:metabolism / Q000502:physiology*; D007502:Iron Chelating Agents / Q000494:pharmacology*; D007538:Isoniazid / Q000031:analogs & derivatives* / Q000494:pharmacology; D009369:Neoplasms / Q000473:pathology*; D011730:Pyridoxal / Q000031:analogs & derivatives* / Q000494:pharmacology; D011990:Receptors, Transferrin / Q000378:metabolism; D013498:Suramin / Q000494:pharmacology*; D014168:Transferrin / Q000378:metabolism
D007502:Iron Chelating Agents; D011990:Receptors, Transferrin; D014168:Transferrin; D011730:Pyridoxal; D013498:Suramin; C021079:pyridoxal isonicotinoyl hydrazone; D004247:DNA; D007501:Iron; D007538:Isoniazid