Barrera G, Pizzimenti S, Serra A, Fazio V M, Canuto R A, Dianzani M U
Dipartimento di Medicina e Oncologia Sperimentale, Università di Torino, Italy.
Cancer Detect Prev. 2000;24(3):244-51.
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.
脂质过氧化会产生多种有毒羰基化合物，包括具有生物活性的醛类。在先前的研究中，我们证明了4-羟基壬烯醛（HNE），脂质过氧化的主要产物之一，可抑制K562和HL-60人白血病细胞的生长及c-myc表达。在本研究中，我们比较了HNE与4-羟基辛烯醛（HOE）、4-羟基十一碳烯醛（HUE；亲脂性尾部长度不同）以及类似醛类2-反式壬醛（缺少羟基）和壬醛（缺少羟基及反式碳碳双键）对HL-60细胞增殖和c-myc表达的影响。HUE和HOE以剂量依赖方式抑制生长及c-myc表达，其效果与HNE相当，而2-壬醛和壬醛不影响这些参数。我们的结果表明，脂质过氧化产生的不同醛类可能通过下调c-myc导致生长抑制，且涉及的分子特征似乎是羟基和反式碳碳双键。
