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Dp44mT, an iron chelator, suppresses growth and induces apoptosis via RORA-mediated NDRG2-IL6/JAK2/STAT3 signaling in glioma.
Zhou, Jinpeng; Jiang, Yang; Zhao, Junshuang; Zhang, Haiying; Fu, Jinlong; Luo, Peng; Ma, Yanju; Zou, Dan; Gao, Huiling; Hu, Jiangfeng; Zhang, Ye; Jing, Zhitao.
Affiliation
  • Zhou J; Department of Neurosurgery, the First Hospital of China Medical University, NO.155, North Nanjing Street, Heping District, Shenyang, 110001, Liaoning Province, People's Republic of China.
  • Jiang Y; Department of Neurosurgery, the First Hospital of China Medical University, NO.155, North Nanjing Street, Heping District, Shenyang, 110001, Liaoning Province, People's Republic of China.
  • Zhao J; Department of Neurosurgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Zhang H; Department of Neurosurgery, the First Hospital of China Medical University, NO.155, North Nanjing Street, Heping District, Shenyang, 110001, Liaoning Province, People's Republic of China.
  • Fu J; International Education College, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, China.
  • Luo P; Department of Neurosurgery, the First Hospital of China Medical University, NO.155, North Nanjing Street, Heping District, Shenyang, 110001, Liaoning Province, People's Republic of China.
  • Ma Y; Department of Neurosurgery, the First Hospital of China Medical University, NO.155, North Nanjing Street, Heping District, Shenyang, 110001, Liaoning Province, People's Republic of China.
  • Zou D; Department of Oncology, Liaoning Province Tumor Hospital, Shenyang, Liaoning, China.
  • Gao H; The First Laboratory of Cancer Institute, the First Hospital of China Medical University, Shenyang, Liaoning, China.
  • Hu J; College of Life and Health Sciences, Northeastern University, Shenyang, Liaoning, China.
  • Zhang Y; Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Jing Z; The First Laboratory of Cancer Institute, the First Hospital of China Medical University, Shenyang, Liaoning, China.
Cell Oncol (Dordr) ; 43(3): 461-475, 2020 Jun.
Article in En | MEDLINE | ID: mdl-32207044
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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Full text: 1 Database: MEDLINE Main subject: Thiosemicarbazones / Iron Chelating Agents / Apoptosis / Tumor Suppressor Proteins / STAT3 Transcription Factor / Janus Kinase 2 / Nuclear Receptor Subfamily 1, Group F, Member 1 / Glioma Type of study: Prognostic_studies Limits: Animals / Female / Humans Language: En Year: 2020 Type: Article
Fulltext
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Full text: 1 Database: MEDLINE Main subject: Thiosemicarbazones / Iron Chelating Agents / Apoptosis / Tumor Suppressor Proteins / STAT3 Transcription Factor / Janus Kinase 2 / Nuclear Receptor Subfamily 1, Group F, Member 1 / Glioma Type of study: Prognostic_studies Limits: Animals / Female / Humans Language: En Year: 2020 Type: Article