Anthocyanins induce cell cycle perturbations and apoptosis in different human cell lines
Anthocyanins induce cell cycle perturbations and apoptosis in different human cell lines
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DOI：
10.1093/carcin/bgh138
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发表时间：
2004-08-01
期刊：
影响因子：
4.7
通讯作者：
Bianchi, L
中科院分区：
文献类型：
--
作者：
Lazzè, MC;Savio, M;Bianchi, L
为了研究花青素的生物学特性的机制基础，两种糖苷配基花青素[飞燕草色素（DY）和矢车菊色素（CY）]被用于检测它们对人癌细胞（子宫癌和结肠腺癌细胞）和正常人成纤维细胞的细胞周期进程和诱导凋亡的影响。这些化合物在分子结构中β环上羟基的数量和位置不同。通过HPLC分析证实了花青素的细胞摄取，并且没有检测到代谢物。克隆形成试验表明，CY仅在成纤维细胞中诱导剂量依赖性生长抑制作用。流式细胞术分析证实了这种效应，显示S期细胞显著减少。相反，DP抑制正常和肿瘤细胞系的细胞生长。在成纤维细胞中，这种情况伴随着S期细胞的积累，表明从S期到G（2）期的转变受阻。另一方面，在肿瘤细胞系中，我们观察到G（1）期细胞减少，并出现了一部分亚二倍体DNA含量的细胞，从而证明了DP的凋亡效应。DP诱导的细胞凋亡的发生通过形态学和生化特征，包括核浓缩和碎裂、膜联蛋白V染色、DNA梯状和聚（ADP-核糖）聚合酶-1-蛋白水解来证实。此外，DP处理后凋亡细胞的线粒体膜电位明显丢失。DP与CY相比所产生的不同作用表明DP分子结构中β环上三个羟基的存在可能对其更大的生物活性很重要。
To investigate the mechanistic basis for the biological properties of anthocyanins, two aglycone anthocyanins [delphinidin (DY) and cyanidin (CY)] were used to examine their effects on cell cycle progression and on induction of apoptosis in human cancer cells (uterine carcinoma and colon adenocarcinoma cells) and in normal human fibroblasts. These compounds differ in the number and position of hydroxyl groups on the beta ring in the molecular structure. Cellular uptake of anthocyanins was confirmed by HPLC analysis and no metabolites were detected. The clonogenic assay showed that CY induces a dose-dependent growth inhibitory effect only in fibroblasts. This effect was confirmed by flow cytometric analysis, showing a significant reduction of cells in S phase. In contrast, DP inhibited cell growth in normal and tumour cell lines. This event is accompanied in fibroblasts by an accumulation of cells in the S phase suggesting a block in the transition from S to G(2) phase. On the other hand, in tumour cell lines we observed a reduction of cells in G(1) phase, paralleled by the appearance of a fraction of cells with a hypodiploid DNA content, thus demonstrating an apoptotic effect by DP. The occurrence of apoptosis induced by DP was confirmed by morphological and biochemical features, including nuclear condensation and fragmentation, annexin V staining, DNA laddering and poly(ADP-ribose) polymerase-1-proteolysis. Furthermore, the mitochondrial membrane potential of apoptotic cells after treatment with DP was significantly lost. The different effects exerted by DP as compared with CY suggest that the presence of the three hydroxyl groups on the beta ring in the molecular structure of DP may be important for its greater biological activity.