Effect of bioactive aldehydes on cell proliferation and c-myc expression in HL-60 human leukemic cells.
Lipid peroxidation produces several toxic carbonyls, including biologically active aldehydes. In previous studies, we demonstrated that 4-hydroxynonenal (HNE), one of the major products of lipoperoxidation, inhibited growth and c-myc expression in K562 and HL-60 human leukemic cells. In this study, we compared the HNE effects with those of 4-hydroxyoctenal (HOE), 4-hydroxyundecenal (HUE; different lengths of the lipophilic tail), and the analogous aldehydes 2-trans-nonanal (lacking the OH group) and nonenal (lacking the OH group and the trans CC double bond), on HL-60 cell proliferation and c-myc expression. HUE and HOE inhibited growth and c-myc expression in a dose-dependent fashion, with an effectiveness comparable with that of HNE, whereas 2-nonenal and nonanal did not affect these parameters. Our results showed that different aldehydes produced from lipid peroxidation may contribute to growth inhibition by c-myc downregulation and that the molecular features involved seem to be the hydroxy group and the trans CC double bond.
Barrera
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Dipartimento di Medicina e Oncologia Sperimentale, Università di Torino, Italy.
Pizzimenti
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Serra
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Fazio
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Canuto
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Dianzani
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D000447:Aldehydes / Q000494:pharmacology*; D015152:Blotting, Northern; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D018922:HL-60 Cells; D006801:Humans; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis*; D012313:RNA / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
D000447:Aldehydes; D016271:Proto-Oncogene Proteins c-myc; C046538:4-hydroxy-2-octenal; C013166:2-nonenal; C046537:4-hydroxy-2-undecenal; D012313:RNA; C027576:4-hydroxy-2-nonenal