Impaired proliferation and DNA synthesis of a human tumor cell line (HeLa) caused by short treatment with the anti-anemic drug jectofer (ferric-sorbitol-citrate) and the lipid peroxidation product 4-hydroxynonenal.
Anti-anaemic drug, ferric-sorbitol-citrate complex (FSC), inhibit tumour cell growth through the mechanisms which are complex and not entirely understood. The probable mechanisms of described effects of iron is iron-induced oxidative stress of the treated cells. Hence, the effects of FSC on HeLa cell growth in vitro were compared with the biological activity of one of the major mediators of the oxygen free radicals--aldehyde 4-hydroxinonenal (HNE), to see if the effects of FSC and of HNE resemble each other. Impaired proliferative ability and DNA synthesis of HeLa cells was observed after treatment with anti-anaemic drug FSC for 24 hours. After treatment with FSC and culturing of HeLa cells in fresh medium for 24 or 96 hours the cells did not proliferate at all, DNA synthesis was transiently recovered and then diminished again. HNE blocked cell proliferation during the time the aldehyde was present in culture and 24 h later. Afterwards, the cells proliferated as control non-treated cells. HNE did not inhibit DNA synthesis during treatment, but intensity of 3H-thymidine incorporation was lower after preincubation. Thus, both FSC and HNE interfere with the basic mechanisms of the cell growth regulation, while antitumour activity of FSC resembles, but does not necessarily include iron induced lipid peroxidation.
Poljak-Blazi
M
M
Rudjer Boskovic Institute, Zagreb, Croatia.
Zarkovic
N
N
Schaur
R J
RJ
D000447:Aldehydes / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects*; D019343:Citric Acid / Q000633:toxicity*; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects*; D004338:Drug Combinations; D005290:Ferric Compounds / Q000633:toxicity*; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D015227:Lipid Peroxidation; D013012:Sorbitol / Q000633:toxicity*; D013936:Thymidine / Q000378:metabolism; D013997:Time Factors
D000447:Aldehydes; D004338:Drug Combinations; D005290:Ferric Compounds; C008170:citric acid, iron, sorbitol drug combination; D019343:Citric Acid; D013012:Sorbitol; D004247:DNA; C027576:4-hydroxy-2-nonenal; D013936:Thymidine