Department of Medicine and Experimental Oncology, University of Turin, Torino, Italy.
J Nutr Biochem. 2010 Sep;21(9):818-26. doi: 10.1016/j.jnutbio.2009.06.005. Epub 2009 Sep 3.
The effects of polyunsaturated fatty acids (PUFAs) obtained from the diet on colorectal cancer have been widely explored. However, controversial results have been obtained about the role played by the lipid peroxidation products of PUFAs, such as 4-hydroxy-nonenal (HNE), in the control of colon cancer growth. This aldehyde, indeed, showed both procarcinogenic and protective effects. In an attempt to verify the action of HNE, we studied the effects of a low dose of HNE (1 microM), similar to those "physiologically" found in normal cells and plasma, on telomerase activity, a key parameter of malignant transformation. Caco-2 cells were exposed to HNE and, paralleling cell growth inhibition, we observed the down-regulation of telomerase activity and hTERT expression. Similar effects have also been observed in HT-29 cells, in which HNE inhibited cell proliferation, telomerase activity and hTERT expression, suggesting that the inhibition of telomerase activity could be a general mechanism involved in the antiproliferative effect exerted by this aldehyde. Finally, we elucidated the mechanism of hTERT inhibition by HNE. A reduction of GSH content preceded the decrease of telomerase activity, but this only partially explained the telomerase activity inhibition. The major mechanism of HNE action seems to be the modulation of expression and activity of transcription factors belonging to the Myc/Mad/Max network. Since the presence of PUFAs in the diet exposes epithelial colon cells to HNE, this aldehyde could contribute to cell growth control through the inhibitory action on telomerase activity and hTERT expression, suggesting a protective effect on colon mucosa.
饮食中多不饱和脂肪酸（PUFAs）对结直肠癌的影响已经得到广泛研究。然而，关于多不饱和脂肪酸脂质过氧化产物，如 4-羟基壬烯醛（HNE），在控制结肠癌生长中的作用，研究结果存在争议。事实上，这种醛既具有致癌作用，又具有保护作用。为了验证 HNE 的作用，我们研究了低剂量 HNE（1 microM）的作用，该剂量类似于正常细胞和血浆中“生理上”发现的剂量，对端粒酶活性这一恶性转化的关键参数的影响。Caco-2 细胞暴露于 HNE 后，我们观察到细胞生长抑制与端粒酶活性下调和 hTERT 表达下调平行。在 HT-29 细胞中也观察到类似的效应，HNE 抑制细胞增殖、端粒酶活性和 hTERT 表达，表明端粒酶活性的抑制可能是这种醛发挥抗增殖作用的一般机制。最后，我们阐明了 HNE 抑制 hTERT 的机制。GSH 含量的减少先于端粒酶活性的降低，但这仅部分解释了端粒酶活性的抑制。HNE 的主要作用机制似乎是调节属于 Myc/Mad/Max 网络的转录因子的表达和活性。由于饮食中 PUFAs 的存在使结肠上皮细胞暴露于 HNE 中，因此这种醛可能通过抑制端粒酶活性和 hTERT 表达来控制细胞生长，从而对结肠黏膜起到保护作用。
