白花丹提取物在癌细胞系中的体外研究。
In-vitro Studies of Extracts of Plumbago Zeylanica in Cancer Cell Lines.
发表日期:2024 Jul 09
作者:
Fathima Nausheen Usman, Naveen Kumar Singhal
来源:
Cell Death & Disease
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,但全球结直肠癌的发病率仍在上升。因此,仍然迫切需要确定在预防和/或治疗方案中具有增强功效的新药剂。我们的研究重点是使用白花丹素(一种天然植物化学物质,对其他肿瘤类型显示出良好的效果),以确定其在模拟原发性肿瘤环境(附加培养条件)的实验方案中阻止结肠癌细胞增殖和存活的有效性,以及在循环肿瘤细胞中(未附着条件)。在两种实验设置下,将 HCT116 细胞暴露于低微摩尔范围的白花丹素浓度下,导致细胞周期停滞在 G1 期,通过线粒体细胞死亡途径发生细胞凋亡,并增加活性氧的产生。细胞周期效应在贴壁细胞中更明显,而细胞死亡的诱导在未贴壁细胞中更明显。这些效应与白花丹素对一组已知在细胞周期动力学、凋亡机制和细胞增殖的调节中发挥关键作用的蛋白质的表达水平引起的改变的性质和程度是一致的。鉴于之前报道的白花丹素对正常结肠细胞无毒性,并且在我们的研究中观察到对结肠癌细胞具有显着的抗存活作用,白花丹素应被认为是治疗结肠癌的一种有前景的药物。
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.