Docosahexaenoic acid, a major constituent of fish oil diets, prevents activation of cyclin dependent kinases and S-phase entry by serum stimulation in HT-29 cells
Docosahexaenoic acid, a major constituent of fish oil diets, prevents activation of cyclin dependent kinases and S-phase entry by serum stimulation in HT-29 cells
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DOI：
10.1054/plef.2000.0239
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发表时间：
2001-01-01
影响因子：
3
通讯作者：
Istfan, NW
中科院分区：
文献类型：
--
作者：
Chen, ZY;Istfan, NW
细胞增殖受细胞周期进程的调控，而细胞周期进程又受多种细胞周期蛋白依赖性蛋白激酶(CDKs)的顺序激活控制。为了探讨长链多不饱和脂肪酸(PUFA)影响肿瘤细胞生长的机制(S)，我们比较了不同的n-3和n-6脂肪酸对CDKs活性的影响。二十二碳六烯酸(DHA)是鱼油饲料中的主要成分，能够降低血清刺激的同步化-HT-29细胞中细胞周期蛋白D-1、E-和A相关的激酶活性。DHA对细胞周期蛋白A相关激酶活性的抑制作用具有时间依赖性，可能是通过下调细胞周期蛋白A的表达来实现的。此外，DHA还抑制血清刺激引起的pRb的磷酸化和E2F-1的DNA结合活性，并阻止血清刺激的HT-29细胞进入S期。这些结果表明，DHA可能通过抑制G(1)相关细胞周期调节蛋白的激活和表达而对肿瘤细胞的生长产生负面影响。由于合成抗氧化剂BHT能够剂量依赖地逆转DHA对血清刺激的细胞周期蛋白A/CDK活化的抑制作用，因此，由脂质过氧化产生的内源性氧化应激可能参与了细胞周期进程的控制。(C)2001哈考出版有限公司。
Cellular proliferation is regulated by cell cycle progression which, in turn, is controlled by sequential activation of various cyclin-dependent kinases (CDKs). To explore the mechanism(s) by which long chain polyunsaturated fatty acids (PUFAs) influence the growth of tumor cells, we compared the effects of different n-3 and n-6 fatty acids on the activity of CDKs. Docosahexaenoic acid (DHA), a major component of fish oil diets, is able to reduce serum-stimulated cyclin D-1-, E-, and A- associated kinases activity in synchronized-HT-29 cells. The inhibitory effect of DHA on cyclin A-associated kinase activity is time-dependent, and is probably modulated by down-regulation of cyclin A protein expression. In addition, DHA inhibits the phosphorylation of pRb and DNA-binding activity of E2F-1 in response to serum stimulation, and prevents the serum-stimulated entry of S-phase in HT-29 cells. These results indicate that DHA may exert its negative effect on the growth of tumor cells by inhibiting the activation and expression of G(1)-associated cell cycle regulatory proteins. Since the synthetic antioxidant BHT is able to reverse the inhibition of serum-stimulated activation of cyclin A/CDK by DHA in a dose-dependent manner, endogenous oxidative stress produced by lipid peroxidation in HT-29 cells may be involved in the control of cell cycle progression. (C) 2001 Harcourt Publishers Ltd.