Click Quantitative Mass Spectrometry Identifies PIWIL3 as a Mechanistic Target of RNA Interference Activator Enoxacin in Cancer Cells

J Am Chem Soc. 2017 Feb 1;139(4):1400-1403. doi: 10.1021/jacs.6b11751. Epub 2017 Jan 23.

Abstract

Enoxacin is a small molecule that stimulates RNA interference (RNAi) and acts as a growth inhibitor selectively in cancer but not in untransformed cells. Here, we used alkenox, a clickable enoxacin surrogate, coupled with quantitative mass spectrometry, to identify PIWIL3 as a mechanistic target of enoxacin. PIWIL3 is an Argonaute protein of the PIWI subfamily that is mainly expressed in the germline and that mediates RNAi through piRNAs. Our results suggest that cancer cells re-express PIWIL3 to repress RNAi through miRNAs and thus open a new opportunity for cancer-specific targeting.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Argonaute Proteins / analysis*
  • Argonaute Proteins / antagonists & inhibitors
  • Argonaute Proteins / metabolism
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Proliferation / drug effects
  • Enoxacin / chemistry
  • Enoxacin / pharmacology*
  • Female
  • Humans
  • MCF-7 Cells
  • Mass Spectrometry
  • Molecular Structure

Substances

  • Argonaute Proteins
  • HIWI3 protein, human
  • Enoxacin