Uutpatient Department, the First Affiliated Hospital of Jinzhou Medical University, Jinzhou, People's Republic of China.
Department of Drug Management, the First Affiliated Hospital of Jinzhou Medical University, Jinzhou, People's Republic of China.
Naunyn Schmiedebergs Arch Pharmacol. 2024 Feb;397(2):1115-1125. doi: 10.1007/s00210-023-02668-2. Epub 2023 Aug 23.
Colorectal carcinoma (CRC) is a common cancer associated with poor prognosis, and cudraflavone C (Cud C) is a natural flavonol with reported anti-CRC capacity. However, the precise mechanisms underlying the anti-CRC effect require further demonstration. The aim of present study was to evaluate the impact of Cud C on the cell viability and apoptosis of CRC cells and to determine the underlying mechanisms. The Human Protein Atlas (THPA) and Gene Expression Profiling Interactive Analysis (GEPIA) databases were used to analyze the expression status of glutathione peroxidase 2 (GPX2) in CRC. Cell viability was examined using cell counting kit-8 (CCK-8) assay. Flow cytometry was utilized to evaluate apoptosis. The levels of gene transcription and protein expression of GPX2, caspase-3, cleaved caspase-3), β-catenin, and c-Myc were determined by RT-qPCR and Western blotting. Our results showed that GPX2 was overexpressed in CRC as compared to normal tissue and the extent of GPX2 overexpression is greatest in CRC when compared with other cancers according to GEPIA and THPA databases. GPX2 knockdown significantly suppressed the cell viability, induced apoptosis of CRC cell lines, and restrained the activity of Wnt/β-catenin pathway. Cud C treatment decreased cell viability, induced apoptosis in CRC cell lines, and diminished the expression level of GPX2-dependent activation of Wnt/β-catenin pathway, while such effects can be abolished by GPX2 overexpression. In conclusion, Cud C suppressed GPX2-dependent Wnt/β-catenin pathway to exert anti-CRC function.
结直肠癌（CRC）是一种预后不良的常见癌症，而京尼平苷酸 C（Cud C）是一种具有抗 CRC 能力的天然类黄酮。然而，其抗 CRC 作用的确切机制仍需进一步证实。本研究旨在评估 Cud C 对 CRC 细胞活力和凋亡的影响，并确定其潜在机制。利用人类蛋白质图谱（THPA）和基因表达谱交互分析（GEPIA）数据库分析 CRC 中谷胱甘肽过氧化物酶 2（GPX2）的表达状态。通过细胞计数试剂盒-8（CCK-8）测定细胞活力。采用流式细胞术评估细胞凋亡。通过 RT-qPCR 和 Western blot 测定 GPX2、半胱天冬酶-3、裂解的半胱天冬酶-3、β-连环蛋白和 c-Myc 的基因转录和蛋白表达水平。结果表明，与正常组织相比，CRC 中 GPX2 表达上调，根据 GEPIA 和 THPA 数据库，CRC 中 GPX2 的过表达程度比其他癌症更为显著。GPX2 敲低显著抑制 CRC 细胞系的细胞活力，诱导细胞凋亡，并抑制 Wnt/β-连环蛋白通路的活性。Cud C 处理降低 CRC 细胞系的细胞活力，诱导细胞凋亡，并减弱 GPX2 依赖性 Wnt/β-连环蛋白通路的激活，而过表达 GPX2 可消除这些作用。总之，Cud C 通过抑制 GPX2 依赖性 Wnt/β-连环蛋白通路发挥抗 CRC 功能。
