Abstract：
Despite increased use of early detection methods and more aggressive treatment strategies, the worldwide incidence of colorectal cancer is still on the rise. Consequently, it remains urgent to identify novel agents with enhanced efficacy in prevention and/or therapeutic protocols. Our studies focused on the use of Plumbagin, a natural phytochemical that showed promising results against other tumor types, to determine its effectiveness in blocking the proliferation and survival of colon cancer cells in experimental protocols mimicking the environment in primary tumors (attached culture conditions) and in circulating tumor cells (unattached conditions). Under both experimental settings, exposure of HCT116 cells to Plumbagin concentrations in the low micromolar range resulted in cell cycle arrest at the G1 phase, apoptosis via the mitochondrial cell death pathway, and increased production of reactive oxygen species. The cell cycle effects were more noticeable in attached cells, whereas the induction of cell death was more evident in unattached cells. These effects were consistent with the nature and the magnitude of the alterations induced by Plumbagin on the expression levels of a set of proteins known to play key roles in the regulation of cell cycle dynamics, apoptosis mechanisms and cell proliferation. In light of its previously reported lack of toxicity on normal colon cells and the striking anti-survival effect on colon cancer cells observed in our study, Plumbagin should be considered a promising drug for the treatment of colon cancer.
摘要：
尽管越来越多地使用早期检测方法和更积极的治疗策略，全球结直肠癌的发病率仍在上升。因此,在预防和/或治疗方案中鉴定具有增强疗效的新型药物仍然是当务之急.我们的研究集中在Plumbagin的使用上，一种天然的植物化学物质，对其他类型的肿瘤显示出有希望的结果，以确定其在模拟原发性肿瘤（附着培养条件）和循环肿瘤细胞（未附着条件）的环境的实验方案中阻断结肠癌细胞增殖和存活的有效性。在两种实验设置下，HCT116细胞暴露于低微摩尔浓度的Plumbagin导致细胞周期停滞在G1期,通过线粒体细胞死亡途径，和增加活性氧的产生。细胞周期效应在附着细胞中更为明显，而在未附着的细胞中，细胞死亡的诱导更为明显。这些作用与Plumbagin对一组已知在细胞周期动力学调节中起关键作用的蛋白质的表达水平诱导的改变的性质和程度一致。凋亡机制和细胞增殖。鉴于其先前报道的对正常结肠细胞缺乏毒性以及在我们的研究中观察到的对结肠癌细胞的显着抗存活作用，plumbagin应该被认为是治疗结肠癌的有希望的药物。
