Iron chelator-induced up-regulation of Ndrg1 inhibits proliferation and EMT process by targeting Wnt/β-catenin pathway in colon cancer cells.

Abstract

Di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT), as the novel iron chelator, has been reported to inhibit the tumorigenesis and progression of various cancer cells. However, whether Dp44mT has anticancer effects in colon cancer cells is still unknown. Here, we investigated the antitumor action of Dp44mT in colon cancer and its underlying mechanisms, and the connections between Dp44mT and N-myc downstream-regulated genes 1(Ndrg1). We used cell viability, migration and invasion assay, flow cytometry, western blot and qRT-PCR to examine the anticancer effects of Dp44mT and Ndrg1. We found that Dp44mT suppressed cell viability, migration, invasion and induced apoptosis of colon cancer cells and over-expression of Ndrg1 also suppressed cell viability, migration, invasion and induced apoptosis of colon cancer cells. Dp44mT attenuated the TGF-β1-induced EMT in colon cancer cells, and Dp44mT could up-regulate Ndrg1 expression level. Overexpression of Ndrg1 attenuates the TGF-β1-induced EMT, Dp44mT and Ndrg1 suppressed EMT through activation of Wnt/β catenin signaling pathway. In conclusion, our data demonstrated that Dp44mT/Ndrg1 have effective anticancer capability in colon cancer cells and that may represent a promising treatment strategy for human colon cancer.

• Authors: Zhiqiang Chen, Jing Sun, Tao Li, Yanfeng Liu, Shang Gao, Xuting Zhi, Minhua Zheng
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 506 Issue 1 Pg. 114-121 (11 17 2018) ISSN: 1090-2104 [Electronic] United States
• PMID: 30340826 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Retracted Publication)
• Copyright: Copyright © 2018 Elsevier Inc. All rights reserved.

Chemical References

• Antineoplastic Agents
• CCND1 protein, human
• CTNNB1 protein, human
• Cell Cycle Proteins
• Intracellular Signaling Peptides and Proteins
• Iron Chelating Agents
• N-myc downstream-regulated gene 1 protein
• TGFB1 protein, human
• Thiosemicarbazones
• Transforming Growth Factor beta1
• WNT3A protein, human
• Wnt3A Protein
• beta Catenin
• di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone
• Cyclin D1

Topics

• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects, genetics)
• Cell Cycle Proteins (agonists, genetics, metabolism)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Cyclin D1 (antagonists & inhibitors, genetics, metabolism)
• Epithelial Cells (drug effects, metabolism, pathology)
• Epithelial-Mesenchymal Transition (drug effects, genetics)
• Gene Expression Regulation, Neoplastic
• HCT116 Cells
• Humans
• Intracellular Signaling Peptides and Proteins (agonists, genetics, metabolism)
• Iron Chelating Agents (pharmacology)
• Thiosemicarbazones (pharmacology)
• Transforming Growth Factor beta1 (antagonists & inhibitors, pharmacology)
• Wnt Signaling Pathway (drug effects, genetics)
• Wnt3A Protein (antagonists & inhibitors, genetics, metabolism)
• beta Catenin (antagonists & inhibitors, genetics, metabolism)