Department of Digestive Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
Invest New Drugs. 2021 Apr;39(2):386-393. doi: 10.1007/s10637-020-01006-0. Epub 2020 Sep 30.
Coptis chinensis Franch. has been extensively used in traditional Chinese medicine. The chemical structure of oxyepiberberine, as an alkaloid isolated from Coptis chinensis Franch., has been previously studied. However, anti-cancer effects and underlying mechanisms of oxyepiberberine need to be explored. This study aimed to investigate the anti-cancer effects and underlying mechanisms of oxyepiberberine on LS-1034 human colon cancer cells. The anti-proliferative effects of six derivatives of oxyepiberberine on colon cancer cells were assessed. Among six derivatives, oxyepiberberine showed the greatest anti-proliferative effect on LS-1034 cells with an IC value of 1.36 μM. Oxyepiberberine also induced apoptosis and inhibited migration of LS-1034 cells in a concentration-dependent manner. Importantly, oxyepiberberine was identified as a potent tubulin polymerization inhibitor. The tubulin polymerization inhibitory effects of oxyepiberberine in a concentration-dependent manner with an IC value of 1.26 μM were observed. A xenograft mouse model of colon cancer showed that oxyepiberberine could suppress tumor growth without an obvious toxicity. Conclusion Oxyepiberberine was found as a novel tubulin polymerization inhibitor, and it could be a promising agent to treat colon cancer.
黄连是一种在传统中药中广泛应用的植物。先前研究已经对黄连中分离得到的一种生物碱——小檗碱的化学结构进行了研究。然而，小檗碱的抗癌作用及其潜在机制仍需进一步探索。本研究旨在探讨小檗碱对 LS-1034 人结肠癌细胞的抗癌作用及其潜在机制。评估了小檗碱的六种衍生物对结肠癌细胞的增殖抑制作用。在这六种衍生物中，小檗碱对 LS-1034 细胞的增殖抑制作用最强，IC 值为 1.36 μM。小檗碱还能以浓度依赖性方式诱导 LS-1034 细胞凋亡和抑制迁移。重要的是，小檗碱被鉴定为一种有效的微管蛋白聚合抑制剂。小檗碱以浓度依赖性方式抑制微管蛋白聚合，IC 值为 1.26 μM。结肠癌的异种移植小鼠模型表明，小檗碱能抑制肿瘤生长而无明显毒性。结论小檗碱被发现是一种新型的微管蛋白聚合抑制剂，可能是治疗结肠癌的一种有前途的药物。
