Jafari Naser, Zargar Seyed Jalal, Delnavazi Mohammad-Reza, Yassa Narguess
Department of Cell & Molecular Biology, School of Biology, College of Science, University of Tehran, Tehran, Iran.
Department of Pharmacognosy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Anticancer Agents Med Chem. 2018;18(4):610-616. doi: 10.2174/1871520618666171219121449.
In the present study, we analyzed anti-proliferative and apoptosis induction activity of five phenolic compounds: echisoside, pleoside, chlorogenic acid, 4,5-Di-O-caffeoylquinic acid, and cynarin on AGS (adenocarcinoma gastric) cell line.
These phenolic compounds were isolated from methanol extract of Dorema glabrum root. An MTT assay was conducted to evaluate the inhibitory effect on cancer cells. EB/AO staining was done to assess the mode of cell death and morphological changes of the cells' nuclei. Cell cycle distribution of the cells was analyzed by flow cytometry, and for further confirmation of the pathway, mRNA levels of apoptosis cascade players were quantified by qRT-PCR.
We found that echisoside, pleoside, chlorogenic acid, 4,5-Di-O-caffeoylquinic acid, and cynarin inhibited the proliferation of AGS cancer cells in vitro. Our data revealed that these compounds triggered morphological changes characteristic of apoptotic cell death. These compounds up-regulated bax and caspase3 expression and down-regulated cyclin D1, bcl2, VEGFA, c-myc and survivin. Moreover, cell population increased at the G1 phase, and a number of cells at the G2/M phase of the cell cycle decreased after treatment.
All these data suggest that phenolic compounds have a cytotoxic effect on gastric cancer cells and could trigger apoptosis. Besides cytotoxic activity, they could potentially arrest the cell cycle at the G1 phase.
在本研究中，我们分析了五种酚类化合物——蛇床子苷、波叶大黄苷、绿原酸、4,5-二-O-咖啡酰奎宁酸和洋蓟素对AGS（胃腺癌）细胞系的抗增殖和诱导凋亡活性。
这些酚类化合物从光果阿魏根的甲醇提取物中分离得到。进行MTT试验以评估对癌细胞的抑制作用。采用EB/AO染色来评估细胞死亡模式和细胞核的形态变化。通过流式细胞术分析细胞的细胞周期分布，为进一步确认该途径，通过qRT-PCR对凋亡级联反应相关蛋白的mRNA水平进行定量。
我们发现蛇床子苷、波叶大黄苷、绿原酸、4,5-二-O-咖啡酰奎宁酸和洋蓟素在体外抑制AGS癌细胞的增殖。我们的数据显示这些化合物引发了凋亡性细胞死亡的特征性形态变化。这些化合物上调了bax和caspase3的表达，下调了细胞周期蛋白D1、bcl2、VEGFA、c-myc和survivin的表达。此外，处理后G1期细胞数量增加，细胞周期G2/M期的细胞数量减少。
所有这些数据表明酚类化合物对胃癌细胞具有细胞毒性作用，并可引发凋亡。除细胞毒性活性外，它们还可能使细胞周期停滞在G1期。
