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Abstract：
Colorectal cancer mortality rate and highly altered proteins from the Wnt/β-catenin pathway increase the scientific community\'s interest in finding alternatives for prevention and treatment. This study aims to determine the biological effect of chlorogenic acid (CGA) on two colorectal cancer cell lines, HT-29 and SW480, and its interactions with β-catenin and LRP6 to elucidate a possible modulatory mechanism on the Wnt/β-catenin pathway. These effects were determined by propidium iodide and DiOC6 for mitochondrial membrane permeability, MitoTracker Red for mitochondrial ROS production, DNA content for cell distribution on cell cycle phases, and molecular docking for protein-ligand interactions and binding affinity. Here, it was found that CGA at 2000 µM significantly affects cell viability and causes DNA fragmentation in SW480 cells rather than in HT-29 cells, but in both cell lines, it induces ROS production. Additionally, CGA has similar affinity and interactions for LRP6 as niclosamide but has a higher affinity for both β-catenin sites than C2 and iCRT14. These results suggest a possible modulatory role of CGA over the Wnt/β-catenin pathway in colorectal cancer.
摘要：
结直肠癌死亡率和来自Wnt/β-catenin途径的高度改变的蛋白质增加了科学界对寻找预防和治疗替代方法的兴趣。本研究旨在确定绿原酸（CGA）对两种结直肠癌细胞株的生物学效应，HT-29和SW480及其与β-catenin和LRP6的相互作用阐明了Wnt/β-catenin通路的可能调节机制。碘化丙啶和DiOC6对线粒体膜通透性的影响，线粒体ROS生产的MitoTracker红，细胞周期阶段细胞分布的DNA含量，以及蛋白质-配体相互作用和结合亲和力的分子对接。这里,发现2000μM的CGA显着影响细胞活力，并导致SW480细胞而不是HT-29细胞中的DNA片段化，但是在两种细胞系中，它诱导ROS产生。此外,CGA对LRP6具有与氯硝柳胺相似的亲和力和相互作用，但对β-连环蛋白位点的亲和力均高于C2和iCRT14。这些结果提示CGA在结直肠癌中可能对Wnt/β-连环蛋白途径起调节作用。
