首页> 外文期刊>The Journal of Nutritional Biochemistry >4-Hydroxynonenal, a lipid peroxidation product of dietary polyunsaturated fatty acids, has anticarcinogenic properties in colon carcinoma cell lines through the inhibition of telomerase activity.
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4-Hydroxynonenal, a lipid peroxidation product of dietary polyunsaturated fatty acids, has anticarcinogenic properties in colon carcinoma cell lines through the inhibition of telomerase activity.

机译:饮食中多不饱和脂肪酸的脂质过氧化产物4-羟基壬烯醛通过抑制端粒酶活性而在结肠癌细胞系中具有抗癌作用。

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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 muM), 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.
机译:从饮食中获得的多不饱和脂肪酸(PUFA)对结直肠癌的作用已得到广泛研究。然而,已经获得关于PUFA的脂质过氧化产物如4-羟基壬烯醛(HNE)在控制结肠癌生长中所起的作用的争议性结果。该醛确实显示出致癌作用和保护作用。为了验证HNE的作用,我们研究了低剂量的HNE(1μM)与端粒酶活性(端粒酶活性)有关,端粒酶活性是正常细胞和血浆中的“生理学”作用,与之相似。 Caco-2细胞暴露于HNE,与细胞生长抑制平行,我们观察到端粒酶活性和hTERT表达的下调。在HT-29细胞中也观察到了相似的作用,其中HNE抑制了细胞增殖,端粒酶活性和hTERT表达,这表明端粒酶活性的抑制可能是该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含量的降低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作用的主要机制似乎是属于Myc / Mad / Max网络的转录因子表达和活性的调节。由于饮食中PUFA的存在会使上皮结肠细胞暴露于HNE,因此该醛可通过对端粒酶活性和hTERT表达的抑制作用来促进细胞生长控制,从而提示对结肠粘膜的保护作用。

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