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Small molecule enoxacin is a cancer-specific growth inhibitor that acts by enhancing TAR RNA-binding protein

Sonia Melo1, Alberto Villanueva, Catia Moutinho

  • 1Cancer Epigenetics and Biology Program, Bellvitge Biomedical Research Institute, 08908 L'Hospitalet, Barcelona, Catalonia, Spain.

Proceedings of the National Academy of Sciences of the United States of America
|March 4, 2011
PubMed

Insights

The antibacterial drug enoxacin boosts tumor-suppressing microRNA production by targeting the TRBP protein. This approach shows cancer-specific growth inhibition in preclinical models, offering a novel therapeutic strategy.

Area of Science:

  • Molecular Biology
  • Oncology
  • Pharmacology

Background:

  • MicroRNAs (miRNAs) are key posttranscriptional regulators of gene expression, crucial for cellular pathways.
  • Dysregulated miRNA production and function are implicated in human tumor development and progression.
  • Restoring tumor-suppressor miRNA expression is a potential anti-cancer therapeutic strategy.

Purpose of the Study:

  • To investigate the potential of the antibacterial compound enoxacin to restore miRNA expression in cancer.
  • To elucidate the mechanism by which enoxacin affects miRNA biosynthesis.
  • To evaluate the anti-cancer efficacy of enoxacin in preclinical models.

Main Methods:

  • Utilized human cell cultures and various mouse cancer models (xenograft, orthotopic, metastatic).
  • Investigated the interaction between enoxacin and the TAR RNA-binding protein 2 (TRBP).
  • Assessed miRNA production and cancer cell growth inhibition in response to enoxacin treatment.

Main Results:

  • Enoxacin enhances the production of tumor-suppressor miRNAs by binding to TRBP.
  • Enoxacin demonstrates a TRBP-dependent and cancer-specific growth-inhibitory effect.
  • Treatment with enoxacin normalized aberrant miRNA expression patterns in cancer cells.

Conclusions:

  • Disrupted miRNA expression is a critical factor in tumorigenesis.
  • Enoxacin represents a novel therapeutic strategy for cancer by restoring miRNA homeostasis.
  • Targeting miRNA biosynthesis pathways offers a promising avenue for cancer treatment.

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