Araguspongine C 通过诱导人肺癌细胞凋亡以及抑制氧化应激、炎症和 EGFR-TK 发挥抗癌活性：一项体外和体内研究。
Anticancer activity of Araguspongine C via inducing apoptosis, and inhibition of oxidative stress, inflammation, and EGFR-TK in human lung cancer cells: An in vitro and in vivo study.
发表日期：2024 Jul
作者：
Zhe Li, Hongjiang Yu, Shaik Althaf Hussain, Rui Yang
来源：
Cell Death & Disease
摘要：
含有表皮生长因子受体 (EGFR) 突变的晚期非小细胞肺癌 (NSCLC) 给新型 EGFR 抑制剂的发现和开发带来了选择性压力。因此，本研究旨在探讨 Araguspongine C (Aragus-C) 作为抗肺癌药物的药理作用。评估 Aragus-C 对 A549 和 H1975 细胞活力的影响。进行了进一步的生化测定，以详细说明 Aragus-C 对 A549 细胞凋亡、细胞周期分析和线粒体膜电位的影响。还进行蛋白质印迹分析以确定A549细胞中EGFR的表达。建立A549细胞肿瘤异种移植小鼠模型，以进一步阐明Aragus-C的药理活性。结果表明，与 H1975 细胞相比，Aragus C 对 A549 细胞表现出显着的抑制活性。已发现 Aragus-C 会诱导 A549 细胞凋亡并促进细胞周期停滞在 G2/M 期。它还显示 A549 细胞中 EGFR 的过度表达减少。 在肿瘤异种移植小鼠模型中，它以剂量依赖性方式显示出肿瘤体积的显着减小，8mg/kg治疗组报道了最大的抑制活性。它还通过降低 TNF-α、IL-1β、IL-6 和 MDA 水平，同时增加超氧化物歧化酶和谷胱甘肽过氧化物酶，表现出显着的抗炎和抗氧化活性。我们已经证明了 Aragus-C 的有效抗肺癌活性，它可以被视为 NSCLC 治疗的潜在治疗选择。© 2024 Wiley periodicals LLC。
The advanced non-small cell lung cancer (NSCLC) that harbors epidermal growth factor receptor (EGFR) mutations has put a selective pressure on the discovery and development of newer EGFR inhibitors. Therefore, the present study intends to explore the pharmacological effect of Araguspongine C (Aragus-C) as anticancer agent against lung cancer. The effect of Aragus-C was evaluated on the viability of the A549 and H1975 cells. Further biochemical assays were performed to elaborate the effect of Aragus-C, on the apoptosis, cell-cycle analysis, and mitochondrial membrane potential in A549 cells. Western blot analysis was also conducted to determine the expression of EGFR in A549 cells. Tumor xenograft mice model from A549 cells was established to further elaborate the pharmacological activity of Aragus-C. Results suggest that Aragus C showed significant inhibitory activity against A549 cells as compared to H1975 cells. It has been found that Aragus-C causes the induction of apoptosis and promotes cell-cycle arrest at the G2/M phase of A549 cells. It also showed a reduction in the overexpression of EGFR in A549 cells. In tumor xenograft mice model, it showed a significant reduction of tumor volume in a dose-dependent manner, with maximum inhibitory activity was reported by the 8 mg/kg treated group. It also showed significant anti-inflammatory and antioxidant activity by reducing the level of TNF-α, IL-1β, IL-6, and MDA, with a simultaneous increase of superoxide dismutase and glutathione peroxidase. We have demonstrated the potent anti-lung cancer activity of Aragus-C, and it may be considered as a potential therapeutic choice for NSCLC treatment.© 2024 Wiley Periodicals LLC.