Arylquins target vimentin to trigger Par-4 secretion for tumor cell apoptosis

Nat Chem Biol. 2014 Nov;10(11):924-926. doi: 10.1038/nchembio.1631. Epub 2014 Sep 14.

Abstract

The tumor suppressor protein prostate apoptosis response-4 (Par-4), which is secreted by normal cells, selectively induces apoptosis in cancer cells. We identified a 3-arylquinoline derivative, designated Arylquin 1, as a potent Par-4 secretagogue in cell cultures and mice. Mechanistically, Arylquin 1 binds vimentin, displaces Par-4 from vimentin for secretion and triggers the efficient paracrine apoptosis of diverse cancer cells. Thus, targeting vimentin with Par-4 secretagogues efficiently induces paracrine apoptosis of tumor cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminoquinolines / administration & dosage
  • Aminoquinolines / chemistry
  • Aminoquinolines / pharmacology*
  • Animals
  • Apoptosis / drug effects*
  • Apoptosis Regulatory Proteins / metabolism*
  • Cells, Cultured
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Molecular Structure
  • Neoplasms / pathology*
  • Paracrine Communication / drug effects
  • Vimentin / antagonists & inhibitors*
  • Vimentin / chemistry

Substances

  • Aminoquinolines
  • Apoptosis Regulatory Proteins
  • Arylquin 1
  • Vimentin
  • prostate apoptosis response-4 protein

Associated data

  • PubChem-Substance/199994745
  • PubChem-Substance/199994746
  • PubChem-Substance/199994747
  • PubChem-Substance/199994748
  • PubChem-Substance/199994749
  • PubChem-Substance/199994750
  • PubChem-Substance/199994751
  • PubChem-Substance/199994752
  • PubChem-Substance/199994753