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首页> 外文期刊>Biochemical Pharmacology >Tangutorine induces p21 expression and abnormal mitosis in human colon cancer HT-29 cells.
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Tangutorine induces p21 expression and abnormal mitosis in human colon cancer HT-29 cells.

机译：Tangutorine在人结肠癌HT-29细胞中诱导p21表达和异常有丝分裂。

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摘要

A novel beta-carboline alkaloid, tangutorine (benz[f]indolo[2,3-a]quinolizidine) was isolated from the leaves of Nitraria tangutorum L. [Duan JA, Williams ID, Che CT, Zhou RH, Zhao RH, Tangutorine: a novel beta-carboline alkaloid from Nitraria tangutorum. Tetrahedron Lett 1999;40:2593-6], and its unique structural characters led us to initiate a study of its potential anti-proliferation activity. The in vitro treatment with low doses of tangutorine slightly stimulated the proliferation of human colon cancer HT29 cells until at concentrations higher than 6.25 microg/ml when the cell numbers, cellular MTT reduction, and cell proliferation by 3H-thymidine incorporation decreased in a dose-dependent manner (IC50=15 microg/ml=48 microM). Morphological studies of cells by fluorescence and electron microscopy did not show features for apoptosis but only large vacuoles, swollen mitochondria and dense cytoskeletal filaments bunching in the cytoplasm. Immunoblotting analysis revealed a dramatic induction of cyclin kinase inhibitor p21 as well as an inhibition of topoisomerase II expression at 25 microg/ml tangutorine, thereby impeding cell progression from S to G2/M phase. Cells accumulated at G1 phase of the cell cycle at concentrations > or =50 microg/ml tangutorine. Interestingly, some cells escaped from prolonged growth arrest without cell division and resulted in binucleated and polyploid G1 cells. Taken all results together, tangutorine induced a p21 suppression of all cyclins and their associated kinases, such as the topoisomerase II, and thus inhibited normal DNA replication and mitosis.
机译：从唐古特白刺的叶子中分离出一种新型的β-咔啉生物碱-橘子碱（benz [f] indolo [2,3-a] quinolizidine）。[Duan JA，Williams ID，Che CT，Zhou RH，Zhao RH，Tangutorine ：来自唐古特白刺的新的β-咔啉生物碱。 Tetrahedron Lett 1999; 40：2593-6]，及其独特的结构特征使我们开始对其潜在的抗增殖活性进行研究。当剂量，剂量和剂量降低后，当细胞数量，细胞MTT减少和3H-胸苷掺入引起的细胞增殖减少时，低剂量的橘皮苷的体外处理会轻微刺激人结肠癌HT29细胞的增殖，直至浓度高于6.25 microg / ml。依赖性方式（IC50 = 15 microg / ml = 48 microM）。通过荧光和电子显微镜对细胞的形态学研究没有显示出凋亡的特征，而仅在细胞质中有大的液泡，线粒体肿胀和密集的细胞骨架丝聚集。免疫印迹分析显示，在25微克/毫升的橘子苷中，细胞周期蛋白激酶抑制剂p21产生了显着诱导，并抑制了拓扑异构酶II的表达，从而阻止了细胞从S期发展到G2 / M期。在细胞周期的G1期积累的浓度>或等于50微克/毫升的橘子精氨酸。有趣的是，一些细胞摆脱了长时间的生长停滞而没有细胞分裂，并导致了双核和多倍体G1细胞。综合所有结果，tangutorine诱导所有细胞周期蛋白及其相关激酶（例如拓扑异构酶II）的p21抑制，从而抑制了正常的DNA复制和有丝分裂。

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