Tobacco Research Institute of Chinese Academy of Agricultural Sciences, Qingdao, China.
Shanghai Tobacco Group Company Limited, Shanghai, China.
Sci Rep. 2017 Oct 3;7(1):12572. doi: 10.1038/s41598-017-12918-y.
Chinese medicines are an important source of secondary metabolites with excellent antitumour activity. Evodia rutaecarpa, from the family Rutaceae, exhibits antitumour activity. Evodiamine (EVO), which was isolated from the fruit of E. rutaecarpa, exhibits robust antitumour activity. However, the antitumour mechanism of EVO remains unclear. In this study, we assessed the growth-inhibiting effect of EVO on two renal carcinoma cell lines. We found that EVO could change the morphology and decrease the viability and proliferation of cells in a time- and concentration-dependent manner in vitro. In addition, transcriptome analysis indicated that EVO can modulate the transcriptome of Caki-1 cells. In total, 7,243 differentially expressed genes were found, among which 3,347 downregulated genes and 3,896 upregulated genes were mainly involved in cell migration, apoptosis, cell cycle, and DNA replication. Furthermore, we demonstrated that EVO can cause apoptosis, arrest cells in the G2/M phase, and regulate the expression of apoptosis- and cell cycle-related genes in Caki-1 cells. Our study reveals the anticancer effects of EVO using cellular and molecular data, and indicates the potential uses of this compound as a resource to characterize the antitumour mechanisms of E. rutaecarpa.
中药是具有优异抗肿瘤活性的次生代谢产物的重要来源。芸香科吴茱萸属植物吴茱萸具有抗肿瘤活性。从吴茱萸果实中分离得到的吴茱萸碱(EVO)具有很强的抗肿瘤活性。然而,EVO 的抗肿瘤机制尚不清楚。本研究评估了 EVO 对两种肾癌细胞系生长的抑制作用。我们发现 EVO 可以在体外时间和浓度依赖性地改变细胞形态并降低细胞活力和增殖。此外,转录组分析表明 EVO 可以调节 Caki-1 细胞的转录组。总共发现了 7243 个差异表达基因,其中下调基因 3347 个,上调基因 3896 个,主要涉及细胞迁移、细胞凋亡、细胞周期和 DNA 复制。此外,我们证明 EVO 可以诱导 Caki-1 细胞凋亡,将细胞阻滞在 G2/M 期,并调节与细胞凋亡和细胞周期相关的基因的表达。本研究使用细胞和分子数据揭示了 EVO 的抗癌作用,并表明该化合物作为一种资源具有潜在的用途,可以阐明吴茱萸的抗肿瘤机制。