Procyanidin B1 Promotes PSMC3-NRF2 Ubiquitination to Induce Ferroptosis in Glioblastoma

原花青素B1促进PSMC3-NRF2泛素化诱导胶质母细胞瘤铁死亡

阅读:3
作者:Wei Gao, Yuan Li, Xiang Lin, Kun Deng, Xinmiao Long, Danyang Li, Meng Huang, Xiangyu Wang, Yucong Xu, Xiaoling She, Minghua Wu

Abstract

NRF2 signaling is a crucial antioxidant defense mechanism against ferroptosis in tumors, and targeting NRF2 is essential for tumor therapy. However, the effectiveness of NRF2 inhibitors remains unexplored. The active ingredients of traditional Chinese medicine serve as important sources of NRF2 inhibitors. In this study, we established an intracranial glioblastoma (GBM) orthotopic model and observed the effects of procyanidin B1 on tumor growth and ferroptosis. Using protein-small-molecule docking, z-stack assay of laser confocal imaging, surface plasmon resonance assay, immunoprecipitation, mass spectrometry, and western blotting, we detected the binding between procyanidin B1 and NRF2 and the effect of PSMC3 on the ubiquitin-dependent degradation of NRF2 in GBM cells. Our results showed that procyanidin B1 acted as a novel NRF2 inhibitor to suppress GBM cell proliferation and prolonged the survival of GBM-bearing mice; it also mediated the interaction between PSMC3 and NRF2 to promote ubiquitin-dependent protein degradation of NRF2, which induced ferroptosis in GBM cells. In addition, we found that procyanidin B1 enhanced H&sub2;O&sub2; accumulation by downregulating NRF2 during ferroptosis in GBM cells. The botanical agent procyanidin B1 induced ferroptosis and exerted anti-tumor effects through PSMC3-mediated ubiquitin-dependent degradation of NRF2 proteins, providing a potential drug candidate for adjuvant therapy in patients with GBM.

特别声明

1、本文转载旨在传播信息,不代表本网站观点,亦不对其内容的真实性承担责任。

2、其他媒体、网站或个人若从本网站转载使用,必须保留本网站注明的“来源”,并自行承担包括版权在内的相关法律责任。

3、如作者不希望本文被转载,或需洽谈转载稿费等事宜,请及时与本网站联系。

4、此外,如需投稿,也可通过邮箱info@biocloudy.com与我们取得联系。