Department of Biochemistry, Falavarjan Branch, Islamic Azad University, Isfahan, Iran.
Department of Biochemistry, Falavarjan Branch, Islamic Azad University, Isfahan, Iran.
Toxicol Appl Pharmacol. 2023 Sep 15;475:116626. doi: 10.1016/j.taap.2023.116626. Epub 2023 Jul 10.
A more pronounced characteristic of cancer cells is the energy dependence on glucose, which mitigated by glucose transporters. The comprehension of the regulatory mechanisms behind the Warburg effect holds promise for developing therapeutic interventions for cancers. Studies are lacking which targeted the GLUTs for treatment of malignancy of thyroid tumors. In our current investigation, we have undertaken this study to determine the potential of Apigenin, plant derived flavonoid in modulating tumor apoptosis by targeting GLUTs expression in SW1736 cell line of anaplastic thyroid carcinoma.
Flow cytometry with propidium iodide staining was used to determine cell apoptosis. For glucose uptake detection, the "GOD-PAP" enzymatic colorimetric test was used to measure the direct glucose levels inside the cells. To determine the expression of GLUT1 and GLUT3 mRNA in the SW1736 cell line qRT-PCR was employed. Protein levels of GLUT1 and GLUT3 in the SW1736 cell line were detected with western blotting. Also, the scratch wound healing assay was conducted for cell migration.
According to qRT-PCR analysis, the levels of GLUT1 and GLUT3 mRNA were lower in the group that received Apigenin relative to the control group. The Apigenin treatment of SW1736 cells decreased protein expression of the GLUT1 and GLUT3 levels in conformity to qRT-PCR. The scratch assays revealed that Apigenin treatment of cancer cell lines inhibited cell migration as compared to control.
These findings demonstrate the possibility of targeting the glucose facilitators' pathway for making thyroid cancer cells more susceptible to programmed cell death.
癌细胞的一个更显著特征是对葡萄糖的能量依赖性，这种依赖性可以通过葡萄糖转运蛋白来缓解。对沃伯格效应背后的调控机制的理解有望为癌症的治疗干预提供新的途径。目前缺乏针对葡萄糖转运蛋白治疗甲状腺肿瘤恶性肿瘤的研究。在我们目前的研究中，我们已经着手研究，以确定芹菜素（一种来源于植物的类黄酮）通过靶向甲状腺未分化癌 SW1736 细胞系中的 GLUTs 表达来调节肿瘤细胞凋亡的潜力。
碘化丙啶染色的流式细胞术用于确定细胞凋亡。为了检测葡萄糖摄取，使用“GOD-PAP”酶比色法来测量细胞内的直接葡萄糖水平。为了确定 SW1736 细胞系中 GLUT1 和 GLUT3 mRNA 的表达，采用 qRT-PCR 进行检测。采用 Western blot 检测 SW1736 细胞系中 GLUT1 和 GLUT3 的蛋白水平。此外，还进行了划痕愈合试验来检测细胞迁移。
根据 qRT-PCR 分析，与对照组相比，接受芹菜素处理的 SW1736 细胞中 GLUT1 和 GLUT3 mRNA 的水平较低。芹菜素处理 SW1736 细胞降低了 GLUT1 和 GLUT3 蛋白水平，与 qRT-PCR 结果一致。划痕试验显示，与对照组相比，芹菜素处理的癌细胞系抑制了细胞迁移。
这些发现表明，靶向葡萄糖转运蛋白途径可能使甲状腺癌细胞更容易发生程序性细胞死亡。
