PUBLICATION
Effect of Copper Chelators via the TGF-β Signaling Pathway on Glioblastoma Cell Invasion
- Authors
- Kim, H., Jo, S., Kim, I.G., Kim, R.K., Kahm, Y.J., Jung, S.H., Lee, J.H.
- ID
- ZDB-PUB-221224-28
- Date
- 2022
- Source
- Molecules 27(24): (Journal)
- Registered Authors
- Jung, Seung-Hyun
- Keywords
- D-penicillamine, EMT, copper, glioblastoma, triethylenetetramine, zebrafish
- MeSH Terms
-
- Animals
- Brain Neoplasms*/metabolism
- Cell Line, Tumor
- Cell Movement
- Chelating Agents/pharmacology
- Copper/pharmacology
- Copper Sulfate/pharmacology
- Epithelial-Mesenchymal Transition
- Glioblastoma*/metabolism
- Signal Transduction
- Transforming Growth Factor beta/pharmacology
- Zebrafish
- PubMed
- 36557987 Full text @ Molecules
Citation
Kim, H., Jo, S., Kim, I.G., Kim, R.K., Kahm, Y.J., Jung, S.H., Lee, J.H. (2022) Effect of Copper Chelators via the TGF-β Signaling Pathway on Glioblastoma Cell Invasion. Molecules. 27(24):.
Abstract
Glioblastoma multiforme (GBM) is a fast-growing and aggressive type of brain cancer. Unlike normal brain cells, GBM cells exhibit epithelial-mesenchymal transition (EMT), which is a crucial biological process in embryonic development and cell metastasis, and are highly invasive. Copper reportedly plays a critical role in the progression of a variety of cancers, including brain, breast, and lung cancers. However, excessive copper is toxic to cells. D-penicillamine (DPA) and triethylenetetramine (TETA) are well-known copper chelators and are the mainstay of treatment for copper-associated diseases. Following treatment with copper sulfate and DPA, GBM cells showed inhibition of proliferation and suppression of EMT properties, including reduced expression levels of N-cadherin, E-cadherin, and Zeb, which are cell markers associated with EMT. In contrast, treatment with copper sulfate and TETA yielded the opposite effects in GBM. Genes, including TGF-β, are associated with an increase in copper levels, implying their role in EMT. To analyze the invasion and spread of GBM, we used zebrafish embryos xenografted with the GBM cell line U87. The invasion of GBM cells into zebrafish embryos was markedly inhibited by copper treatment with DPA. Our findings suggest that treatment with copper and DPA inhibits proliferation and EMT through a mechanism involving TGF-β/Smad signaling in GBM. Therefore, DPA, but not TETA, could be used as adjuvant therapy for GBM with high copper concentrations.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping