Rationally repurposed nitroxoline inhibits preclinical models of Epstein-Barr virus-associated lymphoproliferation

Area of Science:

• Oncology
• Virology
• Pharmacology

Background:

• Drug repurposing leverages existing safety profiles for new therapeutic indications.
• Nitroxoline, an antibiotic, possesses metal-chelating properties and inhibits bromodomain and extraterminal (BET) proteins.
• BET proteins are crucial for oncogene expression and are implicated in Epstein-Barr virus (EBV)-driven lymphoproliferation.

Purpose of the Study:

• To investigate the efficacy of nitroxoline as a repurposed therapeutic agent against EBV-associated lymphoproliferation.
• To evaluate nitroxoline's mechanism of action targeting BET proteins in the context of EBV infection.

Main Methods:

• Utilized cell culture models of EBV-associated lymphoproliferation.
• Employed small animal models to assess tumor growth inhibition.
• Compared nitroxoline's efficacy and onset of action with the established BET inhibitor JQ1.

Main Results:

• Nitroxoline demonstrated significant reduction in both cell proliferation and tumor growth in preclinical models.
• Nitroxoline exhibited a faster onset of action compared to the prototype BET inhibitor JQ1.
• These findings validate nitroxoline's inhibitory effect on BET proteins in EBV-driven cancers.

Conclusions:

• Nitroxoline shows translational promise as a repurposed drug for treating EBV-associated lymphoproliferative disorders.
• The study highlights the potential of targeting BET proteins with nitroxoline for cancer therapy.
• Rational drug repurposing of nitroxoline offers a potentially faster and effective therapeutic strategy.