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Nitroxoline induces cell apoptosis by inducing MDM2 degradation in small-cell lung cancer

Jin-Guo Yu1, Cheng-Hong Ji1, Min-Hua Shi1

  • 1Department of Respiratory Medicine, The Second Affiliated Hospital of Soochow University, Suzhou, China.

The Kaohsiung Journal of Medical Sciences
|March 22, 2019
PubMed

Insights

The anti-infective drug nitroxoline (NXQ) inhibits small-cell lung cancer (SCLC) by targeting MDM2. This leads to increased p53 levels, promoting cancer cell death and suggesting NXQ as a potential SCLC therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • MDM2 is a proto-oncogene and E3 ubiquitin ligase promoting tumor formation by degrading tumor suppressors like p53.
  • Small-cell lung cancer (SCLC) is an aggressive form of lung cancer with limited treatment options.

Purpose of the Study:

  • To investigate the anti-cancer effects of nitroxoline (NXQ) on SCLC cells.
  • To elucidate the molecular mechanisms underlying NXQ's anti-SCLC activity, focusing on the MDM2/p53 pathway.

Main Methods:

  • Screening of anti-infective drugs for SCLC cell survival inhibition.
  • Analysis of apoptosis-related proteins (Bcl-2, MCL1, Bim) expression.
  • Investigation of MDM2 and p53 expression and degradation following NXQ treatment.
  • Assessment of MDM2 overexpression effects on NXQ cytotoxicity.

Main Results:

  • Nitroxoline (NXQ) effectively inhibited SCLC cell survival and induced apoptosis.
  • NXQ suppressed antiapoptotic proteins (Bcl-2, MCL1) and upregulated proapoptotic Bim.
  • NXQ induced proteasomal degradation of MDM2, leading to increased p53 expression.
  • Overexpression of MDM2 attenuated NXQ's cytotoxicity in SCLC cells.

Conclusions:

  • NXQ exhibits anti-SCLC activity by downregulating MDM2 expression and subsequently upregulating p53.
  • The MDM2/p53 axis is a key target for NXQ's anti-cancer effects in SCLC.
  • Anti-infective NXQ shows potential as a therapeutic agent for SCLC treatment.
Keywords:
MDM2cell apoptosisnitroxolinep53small-cell lung cancer

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