Department of Biology, Mashhad Branch, Islamic Azad University, Mashhad, Iran.
Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Mol Biol Rep. 2024 Jun 4;51(1):723. doi: 10.1007/s11033-024-09658-4.
Glioblastoma multiforme, a deadly form of brain tumor, is characterized by aggressive growth and poor prognosis. Oxidative stress, a disruption in the balance between antioxidants and oxidants, is a crucial factor in its pathogenesis. Silymarin, a flavonoid extracted from milk thistle, has shown therapeutic potential in inhibiting cancer cell growth, promoting apoptosis, and reducing inflammation. It also regulates oxidative stress. This study aims to investigate the regulatory effects of silymarin on oxidative stress parameters, especially the transcription factor Nrf2 and its related enzymes in GBM cancer cells, to develop a new anti-cancer compound with low toxicity.
First, the cytotoxicity of silymarin on U-87 MG cells was investigated by MTT and the results showed an IC50 of 264.6 μM. Then, some parameters of the redox system were measured with commercial kits, and the obtained results showed that silymarin increased the activity of catalase and superoxide dismutase enzymes, as well as the total antioxidant capacity levels; while the malondialdehyde level that is an indicator of lipid peroxidation was decreased by this compound. The expression level of Nrf2 and HO-1 and glutaredoxin and thioredoxin enzymes were checked by real-time PCR method, and the expression level increased significantly after treatment.
Our findings suggest that silymarin may exert its cytotoxic and anticancer effects by enhancing the Nrf2/HO-1 pathway through antioxidant mechanisms in U-87 MG cells.
多形性胶质母细胞瘤是一种致命的脑瘤,其特征是生长迅速且预后不良。氧化应激是其发病机制中的一个关键因素,它是指抗氧化剂和氧化剂之间的平衡被打破。水飞蓟素是从奶蓟草中提取的一种类黄酮,已显示出抑制癌细胞生长、促进细胞凋亡和减少炎症的治疗潜力。它还可以调节氧化应激。本研究旨在探讨水飞蓟素对氧化应激参数的调节作用,特别是转录因子 Nrf2 及其在 GBM 癌细胞中的相关酶,以开发一种毒性低的新型抗癌化合物。
首先,通过 MTT 法研究了水飞蓟素对 U-87 MG 细胞的细胞毒性,结果显示其 IC50 为 264.6 μM。然后,用商业试剂盒测量了一些氧化还原系统的参数,结果表明水飞蓟素增加了过氧化氢酶和超氧化物歧化酶的活性以及总抗氧化能力水平;而这种化合物降低了丙二醛水平,丙二醛是脂质过氧化的一个指标。通过实时 PCR 法检查了 Nrf2、HO-1、谷胱甘肽还原酶和硫氧还蛋白酶的表达水平,治疗后表达水平显著增加。
我们的研究结果表明,水飞蓟素可能通过增强 U-87 MG 细胞中的 Nrf2/HO-1 通路,通过抗氧化机制发挥其细胞毒性和抗癌作用。