Polyunsaturated fatty acids inhibit telomerase activity in DLD-1 human colorectal adenocarcinoma cells: A dual mechanism approach
Polyunsaturated fatty acids inhibit telomerase activity in DLD-1 human colorectal adenocarcinoma cells: A dual mechanism approach
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DOI：
10.1016/j.bbalip.2005.08.017
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发表时间：
2005-10-15
影响因子：
4.8
通讯作者：
Miyazawa, T
中科院分区：
文献类型：
--
作者：
Eitsuka, T;Nakagawa, K;Miyazawa, T
由于在大多数癌细胞中检测到高端粒酶活性，端粒酶代表了一种有希望的癌症治疗靶点。我们研究了各种脂肪酸对端粒酶的抑制作用，特别强调了具有抗肿瘤特性的脂肪酸，如二十碳五烯酸（EPA）和二十二碳六烯酸（DHA）。为了评价脂肪酸对端粒酶的直接影响，将DLD-1人结肠癌细胞裂解液与样品脂肪酸混合，并测定端粒酶活性。饱和脂肪酸和反式脂肪酸对端粒酶的抑制作用很弱或无抑制作用。与此相反，顺式不饱和脂肪酸显着抑制酶，和抑制效力的增加，双键的数目。因此，多不饱和脂肪酸（PUFA），如EPA和DHA，似乎是强效的端粒酶抑制剂。为了评估转录效应，在样品脂肪酸存在下培养DLD-1细胞，随后评估端粒酶活性和基因表达。培养DLD-1细胞与EPA或DHA导致端粒酶活性显着下降。EPA和DHA通过抑制蛋白激酶C下调人端粒酶逆转录酶（hTERT）和c-myc表达来抑制端粒酶。这些结果表明，PUFAs可以直接抑制端粒酶的酶活性，并在转录水平上调节端粒酶。(c)2005 Elsevier B. V.保留所有权利。
As high telomerase activity is detected in most cancer cells, telomerase represents a promising cancer therapeutic target. We investigated the inhibitory effect of various fatty acids on telomerase, with particular emphasis on those with antitumor properties, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). To evaluate the direct effect of fatty acids on telomerase, cell lysates of DLD-1 human colorectal adenocarcinoma cells were mixed with sample fatty acids, and the telomerase activity was determined. Saturated fatty acids and trans-fatty acids showed very weak or no inhibition of telomerase. In contrast, cis-unsaturated fatty acids significantly inhibited the enzyme, and the inhibitory potency was elevated with an increase in the number of double bonds. Accordingly, polyunsaturated fatty acids (PUFAs), like EPA and DHA, appeared to be powerful telomerase inhibitors. To assess the transcriptional effect, DLD-1 cells were cultured in the presence of sample fatty acids, and telomerase activity and gene expression were subsequently evaluated. Culturing DLD-1 cells with either EPA or DHA resulted in a remarkable decrease in telomerase activity. EPA and DHA inhibited telomerase by down-regulating human telomerase reverse transcriptase (hTERT) and c-myc expression via protein kinase C inhibition. These results indicate that PUFAs can directly inhibit the enzymatic activity of telomerase as well as modulate the telomerase at the transcriptional level. (c) 2005 Elsevier B.V. All rights reserved.