Malarz Katarzyna, Kuczak Michał, Rurka Patryk, Rawicka Patrycja, Boguszewska-Czubara Anna, Jampilek Josef, Mularski Jacek, Musiol Robert, Mrozek-Wilczkiewicz Anna
Department of Systems Biology and Engineering, Silesian University of Technology, Akademicka 16, Gliwice, 44-100, Poland.
Institute of Physics, University of Silesia in Katowice, 75 Pułku Piechoty 1a, Chorzów, 41-500, Poland.
Sci Rep. 2025 May 8;15(1):16081. doi: 10.1038/s41598-025-99277-1.
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.
这项工作展示了一种2-苯乙烯基喹唑啉衍生物抗癌作用的多方面机制。对与酪氨酸激酶抑制以及在基因和蛋白质水平上对细胞靶点的影响相关的各个方面进行的广泛分析揭示了这种IS20化合物在未来研究中的潜力。本研究详细分析了ABL和SRC激酶之间以一种不明显的方式影响EGFR/mTOR信号通路抑制的关系。该研究得到了使用各种分子生物学技术的实验支持,以证实氧化应激的诱导、G2/M期细胞周期的抑制以及通过凋亡和自噬途径触发细胞死亡。细胞模型包括具有不同p53蛋白状态的模型,这以Ndrg1表达改变的形式影响细胞反应。最后,在体内模型中观察到了IS20具有适当的物理化学性质以实现足够的生物利用度和对身体的毒性。