PDF(Pubmed)
Abstract：
Natural chemicals derived from herbal plants have recently been recognized as potentially useful treatment alternatives owing to their ability to target a wide range of important biological molecules. Cynaroside is one of these natural compounds with promising anticancer activity for numerous tumor types. Nevertheless, the anticancer effects and molecular mechanisms of action of cynaroside on colorectal cancer (CRC) remain unclear. In this study, cynaroside was found to markedly inhibit CRC cell proliferation and colony formation in vitro. Cynaroside also inhibited cell proliferation in vivo and decreased the expression of KI67, a cell nuclear antigen. RNA sequencing revealed 144 differentially expressed genes (DEGs) in HCT116 cells and 493 DEGs in RKO cells that were enriched in the cell cycle signaling pathway. Cell division cycle 25A (CDC25A), a DEG widely enriched in the cell cycle signaling pathway, is considered a key target of cynaroside in CRC cells. Cynaroside also inhibited DNA replication and arrested cells in the G1/S phase in vitro. The expression levels of CDC25A and related G1-phase proteins were significantly elevated after CDC25A overexpression in CRC cells, which partially reversed the inhibitory effect of cynaroside on CRC cell proliferation and G1/S-phase arrest. In summary, cynaroside may be used to treat CRC as it inhibits CDC25A expression.
摘要：
源自草药植物的天然化学物质最近被认为是潜在有用的治疗替代品，因为它们能够靶向广泛的重要生物分子。Cynaroside是这些天然化合物之一，对许多肿瘤类型具有有希望的抗癌活性。然而，西纳苷对大肠癌(CRC)的抗癌作用和分子机制尚不清楚.在这项研究中,发现西纳苷在体外显着抑制CRC细胞增殖和集落形成。Cynaroside还在体内抑制细胞增殖并降低细胞核抗原KI67的表达。RNA测序显示HCT116细胞中的144个差异表达基因(DEGs)和RKO细胞中的493个DEGs在细胞周期信号通路中富集。细胞分裂周期25A（CDC25A），在细胞周期信号通路中广泛富集的DEG，被认为是CRC细胞中cynaroside的关键靶标。Cynaroside还抑制DNA复制并在体外将细胞阻滞在G1/S期。CDC25A过表达后,CRC细胞中CDC25A及相关G1期蛋白的表达水平显著升高,部分逆转了西纳苷对CRC细胞增殖和G1/S期阻滞的抑制作用。总之,cynaroside可用于治疗CRC，因为它抑制CDC25A表达。
