在人体结肠癌细胞中金雀异黄素通过ATM/ p53 依赖型通路诱导 _张志宇 - 金转停_金雀异黄素Genistein

针对病种：结肠癌

发表时间：2013年7月

发表国家：希腊

登载刊物：国际肿瘤学杂志

研究单位：美国芝加哥大学中药研究唐中心等

研究人员：张志宇，王崇智，杜广建，等

主要结论：我们的数据显示，金雀异黄素、大豆苷元和鹰嘴豆芽素表现出对HCT-116/SW-480 结肠癌细胞的生长抑制作用和促进细胞凋亡的效应。金雀异黄素表现出的作用明显大于其他两种化合物，以时间和剂量依赖的方式。这些结果表明，大豆异黄酮，尤其是金雀异黄素，能促进结肠癌细胞的生长抑制作用，促进细胞凋亡和细胞周期在 G2/M 期阻滞。ATM/p53-p21 交叉管理网络可能发挥关键作用，调节金雀异黄素在结肠癌组织中的抗癌活性.

International Journal of Oncology, 2013, 43(1):289-96.

Genistein induces G2/M cell cycle arrest and apoptosis via ATM/p53-dependent pathway in human colon cancer cells

Zhiyu Zhang, Chong Zhi Wang, Guang Jian Du, et al

Tang Center for Herbal Medicine Research, University of Chicago, Chicago, IL 60637, USA; et al

Soybean isoflavones have been used as a potential preventive agent in anticancer research for many years. Genistein is one of the most active flavonoids in soybeans. Accumulating evidence suggests that genistein alters a variety of biological processes in estrogen-related malignancies, such as breast and prostate cancers. However, the molecular mechanism of genistein in the prevention of human colon cancer remains unclear. Here we attempted to elucidate the anticarcinogenic mechanism of genistein in human colon cancer cells. First we evaluated the growth inhibitory effect of genistein and two other isoflavones, daidzein and biochanin A, on HCT-116 and SW-480 human colon cancer cells. In addition, flow cyto-metry was performed to observe the morphological changes in HCT-116/SW-480 cells undergoing apoptosis or cell cycle arrest, which had been visualized using Annexin V-FITC and/or propidium iodide staining. Real-time PCR and western blot analyses were also employed to study the changes in expression of several important genes associated with cell cycle regulation. Our data showed that genistein, daidzein and biochanin A exhibited growth inhibitory effects on HCT-116/SW-480 colon cancer cells and promoted apoptosis. Genistein showed a significantly greater effect than the other two compounds, in a time- and dose-dependent manner. In addition, genistein caused cell cycle arrest in the G2/M phase, which was accompanied by activation of ATM/p53, p21waf1/cip1 and GADD45α as well as downregulation of cdc2 and cdc25A demonstrated by q-PCR and immunoblotting assay. Interestingly, genistein induced G2/M cell cycle arrest in a p53-dependent manner. These findings exemplify that isoflavones, especially genistein, could promote colon cancer cell growth inhibition and facilitate apoptosis and cell cycle arrest in the G2/M phase. The ATM/p53-p21 cross-regulatory network may play a crucial role in mediating the anticarcinogenic activities of genistein in colon cancer.

希腊《国际肿瘤学杂志》，2013年7月

在人体结肠癌细胞中金雀异黄素通过ATM/ p53 依赖型通路诱导 G2/M 期细胞周期中止和细胞凋亡

张志宇，王崇智，杜广建，等

美国芝加哥大学中药研究唐中心等

在多年的抗癌研究中，大豆异黄酮已经被用作潜在的预防药物。金雀异黄素是大豆中最活跃的黄酮类之一。越来越多的证据表明，金雀异黄素改变了雌激素相关的恶性肿瘤各种生物进程，例如乳腺癌和前列腺癌。然而，金雀异黄素在预防人类体肠癌方面的分子机制仍不清楚。这里，我们尝试阐明金雀异黄素对人体结肠癌细胞的抗癌机理。首先，我们评估了金雀异黄素和其他两种大豆异黄酮，大豆黄酮和鹰嘴豆芽素对 HCT-116 和 SW-480 人体结肠癌细胞的生长抑制作用。然后，用流动细胞法观察 HCT-116/SW-480 细胞凋亡或细胞周期阻滞的由于膜联蛋白 V-FITC 和/或碘化丙啶染色可视的形貌变化。采用实时荧光定量 PCR 和免疫印迹分析研究与细胞周期调控有关的几个重要基因表达的变化。我们的数据显示，金雀异黄素、大豆苷元和鹰嘴豆芽素表现出对HCT-116/SW-480 结肠癌细胞的生长抑制作用和促进细胞凋亡的效应。金雀异黄素表现出的作用明显大于其他两种化合物，以时间和剂量依赖的方式。此外，金雀异黄素会导致细胞周期在 G2/M 期阻滞，伴随着 ATM/p53、 p21waf1 /cip1 和 GADD45α的活化，以及由q-聚合酶链反应和免疫印迹法测定的cdc2 和 cdc25A de 下调。有趣的是，金雀异黄素以 p53 依赖的方式诱导 G2/M 期细胞周期阻滞。这些结果表明，大豆异黄酮，尤其是金雀异黄素，能促进结肠癌细胞的生长抑制作用，促进细胞凋亡和细胞周期在 G2/M 期阻滞。ATM/p53-p21 交叉管理网络可能发挥关键作用，调节金雀异黄素在结肠癌组织中的抗癌活性。