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首页> 外文期刊>Drug Design, Development and Therapy >Isobavachalcone isolated from Psoralea corylifolia inhibits cell proliferation and induces apoptosis via inhibiting the AKT/GSK-3β/β-catenin pathway in colorectal cancer cells
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Isobavachalcone isolated from Psoralea corylifolia inhibits cell proliferation and induces apoptosis via inhibiting the AKT/GSK-3β/β-catenin pathway in colorectal cancer cells

机译：分离出的补骨脂中的异巴伐康酮通过抑制大肠癌细胞中的AKT /GSK-3β/β-catenin途径抑制细胞增殖并诱导凋亡

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Background: Colorectal cancer (CRC) is a common form of cancer associated with a high mortality rate and poor prognosis. Given the limited efficacy of current therapies for CRC, interest in novel therapeutic agents isolated from natural sources has increased. We studied the anticancer properties of isobavachalcone (IBC), a flavonoid isolated from the herb Psoralea corylifolia , which is used in traditional Chinese medicine, in an in vitro model of CRC. Materials and methods: Cell viability and growth of CRC cells were determined by Cell Counting Kit-8 and colony formation assays following treatment with varying concentrations of IBC, respectively. Apoptosis was examined by 4′,6-diamidino-2-phenylindole staining and flow cytometry with Annexin V/propidium iodide double staining. Western blot analysis was used to analyze expression of apoptosis-associated protein pathway and the AKT/GSK-3β/β-catenin signaling pathway. Results: Initial experiments showed that IBC inhibited proliferation and colony formation of human CRC cell lines in dose- and time-dependent manners. The antiproliferative effect of IBC resulted from induction of apoptosis, as evidenced by morphological changes in the nucleus, flow cytometry analysis, upregulation of cleaved caspase-3 and cleaved PARP, changes in the ratio of the anti-apoptotic protein Bcl-2 and the pro-apoptotic protein Bax, translocation of Bax from the cytosol to the mitochondria, and decreased expression of two inhibitors of apoptosis family proteins, XIAP, and survivin. Western blot analysis of signaling pathway proteins demonstrated that IBC downregulated Wnt/β-catenin signaling, which has previously been associated with CRC, by inhibiting the AKT/GSK-3β signaling pathway. Conclusion: This study demonstrated that IBC inhibited cell proliferation and induced apoptosis through inhibition of the AKT/GSK-3β/β-catenin pathway in CRC. These results suggest the potential of IBC as a novel therapeutic agent for the treatment of CRC.
机译：背景：大肠癌（CRC）是一种常见的癌症，其死亡率高，预后差。鉴于当前CRC疗法的功效有限，人们对从天然来源分离的新型治疗剂的兴趣增加了。我们研究了异花叶烷（IBC）的抗癌特性，该异黄酮是从中草药Psoralea corylifolia中提取的黄酮，该类黄酮在中枢神经系统的体外模型中。材料和方法：分别用不同浓度的IBC处理后，通过Cell Counting Kit-8和集落形成测定法确定CRC细胞的细胞活力和生长。通过4'，6-二mid基-2-苯基吲哚染色和膜联蛋白V /碘化丙啶双重染色的流式细胞术检查细胞凋亡。用Western blot分析细胞凋亡相关蛋白通路和AKT /GSK-3β/β-catenin信号通路的表达。结果：初步实验表明，IBC以剂量和时间依赖性方式抑制人CRC细胞的增殖和集落形成。 IBC的抗增殖作用是由诱导细胞凋亡引起的，其表现为细胞核形态变化，流式细胞术分析，裂解的caspase-3和裂解的PARP上调，抗凋亡蛋白Bcl-2和pro的比例变化证明了这一点。凋亡蛋白Bax，Bax从胞质溶胶到线粒体的移位以及两种凋亡家族蛋白XIAP和survivin抑制剂的表达降低。信号通路蛋白的蛋白质印迹分析表明，IBC通过抑制AKT /GSK-3β信号通路下调了以前与CRC相关的Wnt /β-catenin信号通路。结论：本研究证明IBC通过抑制CRC中的AKT /GSK-3β/β-catenin途径来抑制细胞增殖并诱导细胞凋亡。这些结果表明，IBC作为治疗CRC的新型治疗剂的潜力。

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