Department of Physiology, Research Institute for Endocrine Sciences, Medical School, Jeonbuk National University, 20 Geonji-ro, Deokjin-gu, Jeonju 54907, Jeollabuk-do, Korea.
Molecules. 2022 Aug 15;27(16):5207. doi: 10.3390/molecules27165207.
Auranofin, as a thioredoxin reductase (TrxR) inhibitor, has promising anti-cancer activity in several cancer types. However, little is known about the inhibitory effect of auranofin on lung cancer cell growth. We, therefore, investigated the antigrowth effects of auranofin in various lung cancer cells with respect to cell death, reactive oxygen species (ROS), and glutathione (GSH) levels. Treatment with 05 µM auranofin decreased cell proliferation and induced cell death in Calu-6, A549, SK-LU-1, NCI-H460, and NCI-H1299 lung cancer cells at 24 h. In addition, 05 µM auranofin increased ROS levels, including O, and depleted GSH levels in these cells. N-acetyl cysteine (NAC) prevented growth inhibition and mitochondrial membrane potential (MMP, ∆Ψm) loss in 3 and 5 µM auranofin-treated Calu-6 and A549 cells at 24 h, respectively, and decreased ROS levels and GSH depletion in these cells. In contrast, L-buthionine sulfoximine (BSO) enhanced cell death, MMP (∆Ψm) loss, ROS levels, and GSH depletion in auranofin-treated Calu-6 and A549 cells. Treatment with 3 and 5 µM auranofin induced caspase-3 activation and poly (ADP ribose) polymerase (PARP) cleavage in Calu-6 and A549 cells, respectively. Both were prevented by NAC, but enhanced by BSO. Moreover, TrxR activity was reduced in auranofin-treated Calu-6 and A549 cells. That activity was decreased by BSO, but increased by NAC. In conclusion, these findings demonstrate that auranofin-induced cell death is closely related to oxidative stress resulted from increased ROS levels and GSH depletion in lung cancer cells.
金诺芬作为一种硫氧还蛋白还原酶（TrxR）抑制剂，在几种癌症类型中具有有前景的抗癌活性。然而，关于金诺芬对肺癌细胞生长的抑制作用知之甚少。因此，我们研究了金诺芬对各种肺癌细胞生长的抗增殖作用，涉及细胞死亡、活性氧（ROS）和谷胱甘肽（GSH）水平。在 24 小时内，用 05 µM 金诺芬处理会降低 Calu-6、A549、SK-LU-1、NCI-H460 和 NCI-H1299 肺癌细胞的增殖并诱导细胞死亡。此外，05 µM 金诺芬增加了这些细胞中的 ROS 水平，包括 O2-和 GSH 水平的耗竭。N-乙酰半胱氨酸（NAC）可预防在 3 和 5 µM 金诺芬处理的 Calu-6 和 A549 细胞中 24 小时时的生长抑制和线粒体膜电位（MMP，∆Ψm）丧失，并降低这些细胞中的 ROS 水平和 GSH 耗竭。相反，L-丁硫氨酸亚砜（BSO）增强了金诺芬处理的 Calu-6 和 A549 细胞中的细胞死亡、MMP（∆Ψm）丧失、ROS 水平和 GSH 耗竭。用 3 和 5 µM 金诺芬处理分别诱导 Calu-6 和 A549 细胞中 caspase-3 的激活和多聚（ADP 核糖）聚合酶（PARP）的切割。这两种情况都被 NAC 预防，但被 BSO 增强。此外，金诺芬处理的 Calu-6 和 A549 细胞中的 TrxR 活性降低。BSO 降低了这种活性，但 NAC 增加了这种活性。总之，这些发现表明金诺芬诱导的细胞死亡与肺癌细胞中 ROS 水平升高和 GSH 耗竭引起的氧化应激密切相关。
