PUBLICATION

Unveiling the role of Ndrg1 gene on the oxidative stress induction behind the anticancer potential of styrylquinazoline derivatives

Authors
Malarz, K., Kuczak, M., Rurka, P., Rawicka, P., Boguszewska-Czubara, A., Jampilek, J., Mularski, J., Musiol, R., Mrozek-Wilczkiewicz, A.
ID
ZDB-PUB-250901-6
Date
2025
Source
Scientific Reports   15: 1608116081 (Journal)
Registered Authors
Keywords
Ndrg1, Anticancer drug, Apoptosis, Autophagy, Iron chelator, Oxidative stress, Styrylquinazoline, p53 protein
MeSH Terms
  • Quinazolines
  • Receptor Protein-Tyrosine Kinases
  • Intracellular Signaling Peptides and Proteins
  • Autophagy
  • Humans
  • Disease Models, Animal
  • Zebrafish
  • Antineoplastic Agents*/chemistry
  • Antineoplastic Agents*/pharmacology
  • Tumor Suppressor Protein p53
  • Animals
  • Apoptosis/drug effects
  • Drug Design
  • Cell Line, Tumor
  • Oxidative Stress*/drug effects
  • Cell Cycle Proteins
  • Cell Cycle/drug effects
  • Signal Transduction*
PubMed
40341822 Full text @ Sci. Rep.
Abstract
This work presents a multifaceted mechanism of the anticancer action of a 2-styrylquinazoline derivative. Extensive analysis of various aspects related to tyrosine kinase inhibition and effects on cellular targets at both the gene and protein levels revealed the potential of this IS20 compound for future research. This study presents a detailed analysis of the relationship between ABL and SRC kinase affecting the inhibition of the EGFR/mTOR signaling pathway in a non-obvious manner. The study was supported by experiments using various molecular biology techniques to confirm the induction of oxidative stress, inhibition of the cell cycle in the G2/M phase and the triggering of cell death via both the apoptosis and autophagy pathways. The cell models included those with different p53 protein status, which affected the cellular response in the form of altered Ndrg1 expression. Finally, the appropriate physicochemical properties of IS20 for adequate bioavailability and toxicity to the body were observed in an in vivo model.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping