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首页> 外文期刊>Biochemical Pharmacology >Effects of structurally related flavonoids on cell cycle progression of human melanoma cells: regulation of cyclin-dependent kinases CDK2 and CDK1.
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Effects of structurally related flavonoids on cell cycle progression of human melanoma cells: regulation of cyclin-dependent kinases CDK2 and CDK1.

机译:结构相关的类黄酮对人黑素瘤细胞细胞周期进程的影响:细胞周期蛋白依赖性激酶CDK2和CDK1的调节。

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摘要

We have investigated the effects of a series of flavonoids on cell proliferation and cell cycle distribution in human melanoma cells OCM-1. Among the compounds that potently inhibited OCM-1 cell proliferation, we show that the presence of a hydroxyl group at the 3'-position of the ring B in quercetin and luteolin, correlated to a G1 cell cycle arrest while its absence in kaempferol and apigenin correlated to a G2 block. Genistein with a hydroxyl at 5-position of the ring A arrested cells in G2 while daidzein which lacks it, induced an accumulation of cells in G1. We demonstrate that flavonoids, which induced a cell cycle block in G1, inhibited the activity of CDK2 by 40-60%. By contrast, those which caused an accumulation of cells in G2/M were without effect. On the other hand, while quercetin, daidzein and luteolin did not alter the activity of CDK1, kaempferol, apigenin and genistein inhibited this kinase by 50-70%. We demonstrate that the up-regulation of the CDK inhibitors p27(KIP1) and p21(CIP1) is likely responsible for the inhibition of CDK2 while inhibition of CDK1 was rather due to the phosphorylation of the kinase on Tyr15 residue.
机译:我们已经研究了一系列类黄酮对人黑素瘤细胞OCM-1中细胞增殖和细胞周期分布的影响。在有效抑制OCM-1细胞增殖的化合物中,我们显示出槲皮素和木犀草素中环B的3'-位置存在羟基,与G1细胞周期停滞相关,而在山奈酚和芹菜素中则不存在与G2块相关。 Genistein在A环的5位带有羟基,将细胞阻滞在G2中,而缺乏大豆黄酮的大豆苷元则诱导了G1中细胞的蓄积。我们证明类黄酮诱导G1中的细胞周期阻滞,抑制CDK2的活性40-60%。相反,那些引起细胞在G2 / M中积累的细胞则没有作用。另一方面,虽然槲皮素,大豆苷元和木犀草素没有改变CDK1的活性,但山奈酚,芹菜素和染料木黄酮却抑制了该激酶50-70%。我们证明,CDK抑制剂p27(KIP1)和p21(CIP1)的上调可能是CDK2抑制的原因,而CDK1的抑制则是由于Tyr15残基上激酶的磷酸化。

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