Abstract 4201: Dp44mT, an iron chelator, suppresses cell growth and invasion by inducing N-myc downstream-regulated gene 1 and inhibiting Wnt/β-catenin signaling in human glioma cells

Abstract

Abstract The iron-chelating agent di-2-pyridylketone 4, 4-dimethyl-3-thiosemicarbazone (Dp44mT) can inhibit cell growth and invasion in some human cancers. However, the precise molecular mechanisms involved remain obscure in the context of glioma. Recent evidence suggests that N-myc downstream-regulated gene (NDRG)1 has an oncogenic role function. In the present study, we investigated whether Dp44mT regulates the NDRG1 expression and thereby inhibits glioma cell growth and invasion. We found that Dp44mT inhibited glioma proliferation and invasion in vitro, and reduced average tumor size and wet weight in a xenograft model. Dp44mT overexpression increased NDRG1 expression; NDRG1 silencing stimulated cell growth and invasion and triggered epithelial-to-mesenchymal transition (EMT). We also found that Dp44mT exerts its anti-tumor activity via inhibition of Wnt/β-catenin signaling. Taken together, these findings suggest that the iron chelator Dp44mT inhibits glioma development and progression both in vitro and in vivo by inducing the expression of NDRG1 and suppressing Wnt/β-catenin signaling. Thus, targeting NDRG1 with Dp44mT can be an effective treatment for glioma. Citation Format: Peng Luo, Ye Zhang, Yang Jiang, Ying Xu, Zhitao Jing. Dp44mT, an iron chelator, suppresses cell growth and invasion by inducing N-myc downstream-regulated gene 1 and inhibiting Wnt/β-catenin signaling in human glioma cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4201.