School of Life Science, Shandong University, Jinan, Shandong 250100, P.R. China.
Department of Neurosurgery and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan 610041, P.R. China.
Int J Oncol. 2017 Aug;51(2):467-477. doi: 10.3892/ijo.2017.4037. Epub 2017 Jun 8.
Glioblastoma is the most common brain cancer in adults. It represents one of the top ten malignant tumors with an average survival time of nine months despite treatments with surgery, radiotherapy and chemotherapy. Curcumin is a phytochemical turmeric isolated from root of the Curcuma longa plant. Accumulating evidence have proved that curcumin targets numerous cancer signaling pathways. The E3 ubiquitin ligase NEDD4, neural precursor cell expressed developmentally downregulated protein 4, is frequently overexpressed in various cancers. However, whether curcumin regulates NEDD4 expression has not been described in human cancers. Therefore, in this study, we explored the roles of NEDD4 in glioma cell proliferation, apoptosis and mobility. We further investigated whether curcumin exerts its antitumor activities via suppressing NEDD4 expression. We found that curcumin reduced the expression of NEDD4 and Notch1 and pAKT, leading to glioma cell growth inhibition, apoptosis, and suppression of migration and invasion. Moreover, deletion of NEDD4 expression enhanced the sensitivity of glioma cells to curcumin treatment. Thus, inactivation of NEDD4 by curcumin could be a promising approach for therapeutic intervention.
胶质母细胞瘤是成人中最常见的脑癌。尽管采用手术、放疗和化疗进行治疗，但它仍是十大恶性肿瘤之一，平均存活时间为九个月。姜黄素是一种从姜黄植物根部分离出来的植物化学物质。越来越多的证据证明姜黄素针对多种癌症信号通路。E3 泛素连接酶 NEDD4，即神经前体细胞表达发育下调蛋白 4，在各种癌症中经常过表达。然而，姜黄素是否调节 NEDD4 的表达在人类癌症中尚未描述。因此，在这项研究中，我们探讨了 NEDD4 在神经胶质瘤细胞增殖、凋亡和迁移中的作用。我们进一步研究了姜黄素是否通过抑制 NEDD4 表达发挥其抗肿瘤活性。我们发现姜黄素降低了 NEDD4 和 Notch1 以及 pAKT 的表达，导致神经胶质瘤细胞生长抑制、凋亡，并抑制迁移和侵袭。此外，NEDD4 表达的缺失增强了神经胶质瘤细胞对姜黄素治疗的敏感性。因此，姜黄素使 NEDD4 失活可能是一种有前途的治疗干预方法。
