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Cellular Oncology
Erschienen in:

23.03.2020 | Original paper

Dp44mT, an iron chelator, suppresses growth and induces apoptosis via RORA-mediated NDRG2-IL6/JAK2/STAT3 signaling in glioma

verfasst von: Jinpeng Zhou, Yang Jiang, Junshuang Zhao, Haiying Zhang, Jinlong Fu, Peng Luo, Yanju Ma, Dan Zou, Huiling Gao, Jiangfeng Hu, Ye Zhang, Zhitao Jing

Erschienen in: Cellular Oncology | Ausgabe 3/2020

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Abstract

Purpose

The iron-chelating agent di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT) has been found to inhibit cell growth and to induce apoptosis in several human cancers. However, its effects and mechanism of action in glioma are unknown.

Methods

Human glioma cell line LN229 and patient-derived glioma stem cells GSC-42 were applied for both in vitro and in vivo xenograft nude mouse experiments. The anti-tumor effects of Dp44mT were assessed using MTS, EdU, TUNEL, Western blotting, qRT-PCR, luciferase reporter, chromatin immunoprecipitation and immunohistochemical assays.

Results

We found that Dp44mT can upregulate the expression of the anti-oncogene N-myc downstream-regulated gene (NDRG)2 by directly binding to and activating the RAR-related orphan receptor (ROR)A. In addition, we found that NDRG2 overexpression suppressed inflammation via activation of interleukin (IL)-6/Janus kinase (JAK)2/signal transducer and activator of transcription (STAT)3 signaling.

Conclusions

Our data indicate that Dp44mT may serve as an effective drug for the treatment of glioma by targeting RORA and enhancing NDRG2-mediated IL-6/JAK2/STAT3 signaling.
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Metadaten
Titel
Dp44mT, an iron chelator, suppresses growth and induces apoptosis via RORA-mediated NDRG2-IL6/JAK2/STAT3 signaling in glioma
verfasst von
Jinpeng Zhou
Yang Jiang
Junshuang Zhao
Haiying Zhang
Jinlong Fu
Peng Luo
Yanju Ma
Dan Zou
Huiling Gao
Jiangfeng Hu
Ye Zhang
Zhitao Jing
Publikationsdatum
23.03.2020
Verlag
Springer Netherlands
Erschienen in
Cellular Oncology / Ausgabe 3/2020
Print ISSN: 2211-3428
Elektronische ISSN: 2211-3436
DOI
https://doi.org/10.1007/s13402-020-00502-y

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