Open AccessNitroxoline induces cell apoptosis by inducing MDM2 degradation in small‐cell lung cancer
Author(s) -
Yu JinGuo,
Ji ChengHong,
Shi MinHua
Publication year - 2019
Publication title -
the kaohsiung journal of medical sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.439
H-Index - 36
eISSN - 2410-8650
pISSN - 1607-551X
DOI - 10.1002/kjm2.12051
Subject(s) - mdm2 , downregulation and upregulation , ubiquitin ligase , cancer research , apoptosis , medicine , cell , oncogene , suppressor , cell growth , protein degradation , ubiquitin , cancer , microbiology and biotechnology , biology , cell cycle , biochemistry , gene
The proto‐oncogene MDM2 is a nuclear‐localized E3 ubiquitin ligase, which promotes tumor formation by targeting tumor suppressor proteins, such as p53, for proteasomal degradation. In this study, the anti‐infective drug nitroxoline (NXQ) was screened out to effectively inhibit cell survival of small‐cell lung cancer (SCLC) cells, and induce SCLC cell apoptosis by suppressing antiapoptotic proteins (such as Bcl‐2 and MCL1) and upregulating proapoptotic protein Bim. In the mechanistic study, NXQ was found to downregulate MDM2 expression by inducing its proteasomal degradation, and thus upregulated p53 expression, which was a substrate protein of MDM2. Moreover, overexpression of MDM2 decreased the cytotoxicity of NXQ on SCLC cells. These results demonstrated that NXQ displayed anti‐SCLC activity by suppressing MDM2 expression, which suggested that anti‐infective NXQ had potential for SCLC treatment by targeting the MDM2/p53 axis.