Zhang Zhuo, Li Jingxia, Willis Daneah, Shi Sophia, Tu Huailu, Costa Max
Division of Environmental Medicine, Department of Medicine, New York University Grossman School of Medicine, 341 E 25th Street, New York, NY 10010, USA.
Int J Mol Sci. 2025 Apr 29;26(9):4207. doi: 10.3390/ijms26094207.
Lung cancer is the leading cause of cancer deaths among American men, even though various treatments are available. The discovery and use of new alternative drugs to treat lung cancers are needed to reduce lung cancer mortality. Phytochemicals are potentially desirable therapeutic agents due to their better safety profiles. Isorhapontigenin (ISO) is an orally bioavailable dietary stilbene. Our studies show that treatment with ISO inhibits human lung cancer cell growth, angiogenesis, invasion, and migration. Neural precursor cell expressed developmentally downregulated 9 (NEDD9), a multi-domain scaffolding protein, regulates various processes crucial for tumorigenesis and metastasis. Our results show that NEDD9 is upregulated in the lung tissues from human lung adenocarcinomas (LUADs) and squamous-cell carcinomas (LUSCs) compared to normal lungs. Overexpression of NEDD9 elevates the invasion and migration of human lung cancer cells. Treatment of human lung cancer cells with ISO decreases NEDD9 protein levels. Our studies have also demonstrated that NEDD9 positively regulates angiogenesis, an essential factor in cancer progression. ISO treatment reduces angiogenesis. Moreover, ISO reduces the protein levels of hypoxia-inducible factor-1α (HIF-1α), a transcription factor critical for angiogenesis. Aberrant high expression of β-Catenin leads to various diseases including cancer. Our results show that ISO treatment reduces the activation of β-Catenin through the downregulation of NEDD9. Studies indicate that ISO decreases NEDD9, causing the suppression of cell growth, angiogenesis, invasion, and migration of human lung cancer cells. ISO is a potent therapeutic agent for lung cancer treatment.
肺癌是美国男性癌症死亡的主要原因，尽管有多种治疗方法可供使用。为了降低肺癌死亡率，需要发现和使用新的替代药物来治疗肺癌。植物化学物质因其更好的安全性而可能成为理想的治疗剂。异丹叶大黄素（ISO）是一种口服生物可利用的膳食芪类化合物。我们的研究表明，ISO治疗可抑制人肺癌细胞的生长、血管生成、侵袭和迁移。神经前体细胞表达发育下调9（NEDD9）是一种多结构域支架蛋白，可调节肿瘤发生和转移的各种关键过程。我们的结果表明，与正常肺组织相比，NEDD9在人肺腺癌（LUAD）和肺鳞状细胞癌（LUSC）的肺组织中上调。NEDD9的过表达提高了人肺癌细胞的侵袭和迁移能力。用ISO处理人肺癌细胞可降低NEDD9蛋白水平。我们的研究还表明，NEDD9正向调节血管生成，这是癌症进展中的一个重要因素。ISO治疗可减少血管生成。此外，ISO可降低缺氧诱导因子-1α（HIF-1α）的蛋白水平，HIF-1α是血管生成的关键转录因子。β-连环蛋白的异常高表达会导致包括癌症在内的各种疾病。我们的结果表明，ISO治疗通过下调NEDD9来降低β-连环蛋白的激活。研究表明，ISO可降低NEDD9，从而抑制人肺癌细胞的生长、血管生成、侵袭和迁移。ISO是一种有效的肺癌治疗剂。
