Palmatine induces G2/M phase arrest and mitochondrial-associated pathway apoptosis in colon cancer cells by targeting AURKA

巴马汀 细胞凋亡 癌症研究 结直肠癌 细胞色素c 活性氧 细胞周期检查点 癌细胞 线粒体 癌症 化学 生物 细胞周期 分子生物学 细胞生物学 药理学 生物化学 遗传学 小檗碱
作者
Xiaojiang Liu,Yaru Zhang,Siqi Wu,Minmin Xu,Youfeng Shen,Min Yu,Jinhua Fan,Sijia Wei,Chaohang Xu,Lu Huang,Han Zhao,Xuegang Li,Xiaoli Ye
出处
期刊:Biochemical Pharmacology [Elsevier]
卷期号:175: 113933-113933 被引量:38
标识
DOI:10.1016/j.bcp.2020.113933
摘要

Studies have shown that palmatine (PAL) has anti-cancer effects. However, the activity and potential mechanisms of PAL against colorectal cancer remain elusive. The results showed that PAL significantly inhibited the proliferation of colon cancer cells in vitro and in vivo without significant effect on non-tumorigenic colon cells. Target prediction and clinical sample database analysis suggested that PAL may contribute to colon cancer cells phase arrest and apoptosis by targeting aurora kinase A (AURKA). Inhibition and overexpression of AURKA proved that PAL induces G2/M phase arrest and apoptosis in colon cancer cells by targeting AURKA. Moreover, PAL promoted intracellular Reactive oxygen species (ROS) production and decreased mitochondrial membrane potential (ΔΨm). PAL reduced the levels of AURKA, Bcl-xl and Bcl2 proteins, and promoted the expression of pro-apoptotic proteins P53, P73, Caspase3 and Caspase9, as well as the increase of cytochrome c (cyt. c) in cell lysates in vitro and in vivo. Together, our study confirmed that PAL induced G2/M phase arrest and mitochondrial-associated pathway apoptosis in colon cancer cells by targeting AURKA. PAL may provide a novel solution for the treatment of colon cancer by serving as a new AURKA inhibitor.
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