谷胱甘肽
氧化应激
烟酰胺腺嘌呤二核苷酸磷酸
活性氧
化学
缺氧(环境)
生物化学
氧气
药理学
细胞生物学
生物
氧化酶试验
酶
有机化学
作者
Fenglan Qin,Huige Zhou,Jiayang Li,Jing Liu,Yaling Wang,Ru Bai,Zhiwei Zhang,Manman Ma,Tao Liu,Fene Gao,Peiyao Du,Xiaoquan Lu,Chunying Chen
标识
DOI:10.1016/j.ejphar.2021.174187
摘要
To keep fast proliferation, tumor cells are exposed to higher oxidative stress than normal cells and they upregulate the amount of some antioxidants such as glutathione (GSH) against reactive oxygen species to maintain the balance. This phenomenon is severe in hypoxic tumor cells. Although researchers have proposed a series of treatment strategies based on regulating the intracellular reactive oxygen species level, few of them are related to the hypoxic tumor. Herein, a novel organic compound (PLC) was designed by using lysine as a bridge to connect two functional small molecules, a hypoxia-responsive nitroimidazole derivative (pimonidazole) and a pH-responsive cinnamaldehyde (CA) derivative. Then, the oxidative stress amplifying ability of PLC in hypoxic tumor cells was evaluated. The acidic microenvironment of tumor can trigger the release of CA to produce reactive oxygen species. Meanwhile, large amount of nicotinamide adenine dinucleotide phosphate (NADPH) can be consumed to decrease the synthesis of GSH during the bio-reduction process of the nitro group in PLC under hypoxic conditions. Therefore, the lethal effect of CA can be amplified for the decrease of GSH. Our results prove that this strategy can significantly enhance the therapeutic effect of CA in the hypoxic tumor cells.
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