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.
|Number of pages||3|
|Journal||Nature Chemical Biology|
|State||Published - Nov 1 2014|
Bibliographical noteFunding Information:
This work was supported by National Center for Research Resources through ‘COBRE Center for Biomedical Research Excellence’ grant P20 RR020171 (to L. Hersh, who is the principal investigator of the study on which D.S.W. is core director), NIH–National Cancer Institute grants R01 CA60872 and R21 CA179283 (to V.M.R.) and University of Kentucky Center for Clinical and Translational Science Drug Discovery Pilot grant (to V.M.R., D.S.W. and C.L.).
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ASJC Scopus subject areas
- Molecular Biology
- Cell Biology