谷胱甘肽
细胞内
细胞凋亡
化学
细胞毒性
癌细胞
癌症
程序性细胞死亡
氧化应激
膜透性
细胞生物学
生物化学
生物
酶
膜
体外
遗传学
作者
Javid Ahmad Malla,Rintu M. Umesh,Saleem Yousf,Shrunal Mane,Shilpy Sharma,Mayurika Lahiri,Pinaki Talukdar
标识
DOI:10.1002/anie.202000961
摘要
Abstract Cancer cells use elevated glutathione (GSH) levels as an inner line of defense to evade apoptosis and develop drug resistance. In this study, we describe a novel 2,4‐nitrobenzenesulfonyl (DNS) protected 2‐hydroxyisophthalamide system that exploits GSH for its activation into free 2‐hydroxyisophthalamide forming supramolecular M + /Cl − channels. Better permeation of the DNS protected compound into MCF‐7 cells compared to the free 2‐hydroxyisophthalamide and GSH‐activatable ion transport resulted in higher cytotoxicity, which was associated with increased oxidative stress that further reduced the intracellular GSH levels and altered mitochondrial membrane permeability leading to the induction of the intrinsic apoptosis pathway. The GSH‐activatable transport‐mediated cell death was further validated in rat insulinoma cells ( INS‐1E ); wherein the intracellular GSH levels showed a direct correlation to the resulting cytotoxicity. Lastly, the active compound was found to restrict the growth and proliferation of 3D spheroids of MCF‐7 cells with efficiency similar to that of the anticancer drug doxorubicin.
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