Endocrinology, Department of Clinical and Experimental Medicine, University of Catania, Garibaldi-Nesima Medical Center, 95122 Catania, Italy.
Surgical Oncology, Garibaldi-Nesima Medical Center, 95122 Catania, Italy.
Int J Mol Sci. 2023 Jul 15;24(14):11509. doi: 10.3390/ijms241411509.
There is much evidence linking oxidative stress to thyroid cancer, and stem cells are thought to play a key role in the tumor-initiating mechanism. Their vulnerability to oxidative stress is unexplored. This study aimed to comparatively evaluate the antioxidant capacity of stem/precursor thyroid cells and mature thyrocytes. Human stem/precursor cells and mature thyrocytes were exposed to increasing concentrations of menadione, an oxidative-stress-producing agent, and reactive oxygen species (ROS) production and cell viability were measured. The expression of antioxidant and detoxification genes was measured via qPCR as well as the total antioxidant capacity and the content of glutathione. Menadione elevated ROS generation in stem/precursor thyroid cells more than in mature thyrocytes. The ROS increase was inversely correlated ( = 0.005) with cell viability, an effect that was partially prevented by the antioxidant curcumin. Most thyroid antioxidant defense genes, notably those encoding for the glutathione-generating system and phase I detoxification enzymes, were significantly less expressed in stem/precursor thyroid cells. As a result, the glutathione level and the total antioxidant capacity in stem/precursor thyroid cells were significantly decreased. This reduced antioxidant defense may have clinical implications, making stem/precursor thyroid cells critical targets for environmental conditions that are not detrimental for differentiated thyrocytes.
有大量证据表明氧化应激与甲状腺癌有关,而干细胞被认为在肿瘤起始机制中发挥关键作用。它们对氧化应激的脆弱性尚未得到探索。本研究旨在比较评估干细胞/前体细胞甲状腺细胞和成熟甲状腺细胞的抗氧化能力。将人干细胞/前体细胞和成熟甲状腺细胞暴露于越来越多的产生氧化应激的试剂甲萘醌中,并测量活性氧 (ROS) 的产生和细胞活力。通过 qPCR 测量抗氧化和解毒基因的表达,以及总抗氧化能力和谷胱甘肽含量。甲萘醌在干细胞/前体细胞甲状腺细胞中产生的 ROS 比在成熟甲状腺细胞中更多。ROS 的增加与细胞活力呈负相关( = 0.005),这一效应部分被抗氧化剂姜黄素所阻止。大多数甲状腺抗氧化防御基因,特别是编码谷胱甘肽生成系统和 I 相解毒酶的基因,在干细胞/前体细胞甲状腺细胞中的表达显著降低。结果,干细胞/前体细胞甲状腺细胞中的谷胱甘肽水平和总抗氧化能力显著降低。这种降低的抗氧化防御可能具有临床意义,使干细胞/前体细胞甲状腺细胞成为对未损害分化甲状腺细胞的环境条件的关键靶标。