二硫仑
癌症
药理学
甲基乙二醛
癌症研究
化学
癌细胞
表皮生长因子受体抑制剂
药品
微尺度热泳
医学
生物化学
酶
内科学
表皮生长因子受体
作者
Qian Wu,Mingyang Zhang,Yuanmei Wen,Peihao He,Qiaojun He,Bo Yang,Li Jiang,Yuan Meng,Ji Cao
标识
DOI:10.1016/j.ejphar.2022.175035
摘要
As a key regulator involved in tumor development and progression, DJ-1 has been proposed as a potential therapeutic target against cancer. Also, the development of DJ-1 inhibitors holds great interests in cancer treatment. In the current study, by utilizing a small molecule covalent compounds library screening, we found that disulfiram (DSF), an FDA-approved chronic alcoholism drug, is a potent DJ-1 inhibitor. Glyoxalase assay and microscale thermophoresis analysis suggested that DSF exhibits strong inhibitory activity and high affinity to DJ-1 protein. Additionally, DSF similarly inhibited the methylglyoxal detoxification function of DJ-1 protein at the intracellular level. Notably, we discovered that DSF could significantly enhance N-(4-hydroxyphenyl) retinamide-based proliferation inhibition and apoptosis induction in different types of cancer cell lines, but not in normal tissue lines. Thus, our data suggest DSF functions as a potential inhibitor targeting DJ-1, which may provide a potential synergistic treatment option for cancer therapy.
科研通智能强力驱动
Strongly Powered by AbleSci AI