Arylquins target vimentin to trigger Par-4 secretion for tumor cell apoptosis
September 14th, 2014 by Ravshan Burikhanov
Nature Chemical Biology 10, 924 (2014). doi:10.1038/nchembio.1631
Authors: Ravshan Burikhanov, Vitaliy M Sviripa, Nikhil Hebbar, Wen Zhang, W John Layton, Adel Hamza, Chang-Guo Zhan, David S Watt, Chunming Liu & Vivek M Rangnekar
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.