大黄素诱导结肠癌细胞凋亡潜在途径的综合分析。
Integrated analysis of potential pathways by which aloe-emodin induces the apoptosis of colon cancer cells.
作者信息
Jiang Dongxiao, Ding Shufei, Mao Zhujun, You Liyan, Ruan Yeping
机构信息
College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, People's Republic of China.
Shaoxing Hospital Of Traditional Chinese Medicine, Shaoxing, 312000, People's Republic of China.
出版信息
Cancer Cell Int. 2021 Apr 27;21(1):238. doi: 10.1186/s12935-021-01942-8.
BACKGROUND
Colon cancer is a malignant gastrointestinal tumour with high incidence, mortality and metastasis rates worldwide. Aloe-emodin is a monomer compound derived from hydroxyanthraquinone. Aloe-emodin produces a wide range of antitumour effects and is produced by rhubarb, aloe and other herbs. However, the mechanism by which aloe-emodin influences colon cancer is still unclear. We hope these findings will lead to the development of a new therapeutic strategy for the treatment of colon cancer in the clinic.
METHODS
We identified the overlapping targets of aloe-emodin and colon cancer and performed protein-protein interaction (PPI), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. In addition, we selected apoptosis pathways for experimental verification with cell viability, cell proliferation, caspase-3 activity, DAPI staining, cell cycle and western blotting analyses to evaluate the apoptotic effect of aloe-emodin on colon cancer cells.
RESULTS
The MTT assay and cell colony formation assay showed that aloe-emodin inhibited cell proliferation. DAPI staining confirmed that aloe-emodin induced apoptosis. Aloe-emodin upregulated the protein level of Bax and decreased the expression of Bcl-2, which activates caspase-3 and caspase-9. Furthermore, the protein expression level of cytochrome C increased in a time-dependent manner in the cytoplasm but decreased in a time-dependent manner in the mitochondria.
CONCLUSION
These results indicate that aloe-emodin may induce the apoptosis of human colon cancer cells through mitochondria-related pathways.
背景
结肠癌是一种恶性胃肠道肿瘤,在全球范围内具有较高的发病率、死亡率和转移率。芦荟大黄素是一种源自羟基蒽醌的单体化合物。芦荟大黄素具有广泛的抗肿瘤作用,由大黄、芦荟等草药产生。然而,芦荟大黄素影响结肠癌的机制仍不清楚。我们希望这些发现将引领临床治疗结肠癌新策略的开发。
方法
我们确定了芦荟大黄素和结肠癌的重叠靶点,并进行了蛋白质-蛋白质相互作用(PPI)、基因本体论(GO)和京都基因与基因组百科全书(KEGG)通路分析。此外,我们选择凋亡通路进行实验验证,通过细胞活力、细胞增殖、半胱天冬酶-3活性、DAPI染色、细胞周期和蛋白质印迹分析来评估芦荟大黄素对结肠癌细胞的凋亡作用。
结果
MTT试验和细胞集落形成试验表明芦荟大黄素抑制细胞增殖。DAPI染色证实芦荟大黄素诱导凋亡。芦荟大黄素上调Bax蛋白水平,降低Bcl-2表达,激活半胱天冬酶-3和半胱天冬酶-9。此外,细胞色素C的蛋白质表达水平在细胞质中呈时间依赖性增加,而在线粒体中呈时间依赖性降低。
结论
这些结果表明芦荟大黄素可能通过线粒体相关途径诱导人结肠癌细胞凋亡。
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