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

Arylquins 靶向波形蛋白以触发 Par-4 分泌,导致肿瘤细胞凋亡

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作者: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

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.

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