Bone Marrow Transplantation Unit, Jordan University Hospital, Amman 11942, Jordan.
Hemostasis and Thrombosis Laboratory, School of Medicine, The University of Jordan, Amman 11942, Jordan.
Molecules. 2023 Jan 26;28(3):1215. doi: 10.3390/molecules28031215.
Cancer is a worldwide health problem and is the second leading cause of death after heart disease. Due to the high cost and severe side effects associated with chemotherapy treatments, natural products with anticancer therapeutic potential may play a promising role in anticancer therapy. The purpose of this study was to investigate the cytotoxic and apoptotic characteristics of the aqueous bulb extract on Caco-2 and COLO-205 colorectal cancer cells. In order to reach such a purpose, the chemical composition was examined using the GC-MS method, and the selective antiproliferative effect was determined in colon cancer cell lines in normal gingival fibroblasts. The intracellular ROS, mitochondrial membrane potential, and gene expression changes in selected genes (, , and genes) were assessed to determine the molecular mechanism of the antitumor effect of the extract. GC-MS results revealed the presence of fifty-seven compounds, and Proscillaridin A was the predominant secondary metabolite in the extract. The IC of . bulb extract on Caco-2, COLO-205, and the normal human gingival fibroblasts were obtained at 0.9 µg/mL, 2.3 µg/mL, and 13.1 µg/mL, respectively. The apoptotic effect assay indicated that the bulb extract induced apoptosis in both colon cancer cell lines. bulb extract was only able to induce statistically significant ROS levels in COLO-205 cells in a dose-dependent manner. The mitochondrial membrane potential (MMP) revealed a significant decrease in the MMP of Caco-2 and COLO-205 to various concentrations of the bulb extract. At the molecular level, RT-qPCR was used to assess gene expression of , , and genes in Caco-2 and COLO-205 cancer cells. The results showed that the expression of pro-inflammatory genes and were upregulated. The apoptotic initiator gene was also upregulated in the Caco-2 cell line and did not reach significance in COLO-205 cells. These results lead to the conclusion that . extract induced cell death in both cell lines and may have the potential to be used in CRC therapy in the future.
癌症是一个全球性的健康问题，是仅次于心脏病的第二大死亡原因。由于化疗治疗的高成本和严重的副作用，具有抗癌治疗潜力的天然产物可能在抗癌治疗中发挥有前途的作用。本研究的目的是研究水芹鳞茎提取物对 Caco-2 和 COLO-205 结肠癌细胞的细胞毒性和凋亡特征。为了达到这个目的，使用 GC-MS 方法检查了化学成分，并在正常牙龈成纤维细胞中确定了结肠癌细胞系中的选择性增殖抑制作用。评估了细胞内 ROS、线粒体膜电位和选定基因（、和 基因）的基因表达变化，以确定提取物的抗肿瘤作用的分子机制。GC-MS 结果表明存在五十七种化合物，其中 Proscillaridin A 是提取物中的主要次生代谢物。. 鳞茎提取物对 Caco-2、COLO-205 和正常人牙龈成纤维细胞的 IC 分别为 0.9 µg/mL、2.3 µg/mL 和 13.1 µg/mL。凋亡效应测定表明，鳞茎提取物在两种结肠癌细胞系中均诱导凋亡。鳞茎提取物仅能以剂量依赖性方式在 COLO-205 细胞中诱导统计学上显著的 ROS 水平。线粒体膜电位（MMP）显示 MMP 在 Caco-2 和 COLO-205 细胞中对鳞茎提取物的各种浓度均显着降低。在分子水平上，使用 RT-qPCR 评估 Caco-2 和 COLO-205 癌细胞中 、 和 基因的基因表达。结果表明，促炎基因 和 的表达上调。凋亡起始基因 在 Caco-2 细胞系中也上调，但在 COLO-205 细胞中未达到显着水平。这些结果得出的结论是，. 鳞茎提取物在两种细胞系中均诱导细胞死亡，并且将来可能有潜力用于 CRC 治疗。
