title: Arylquins target vimentin to trigger Par-4 secretion for tumor cell apoptosis.
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.
authors.affiliation: Department of Radiation Medicine, College of Medicine, University of Kentucky, Lexington, KY 40536.
authors.forename: Ravshan
authors.initials: R
authors.lastname: Burikhanov
authors.affiliation: Department of Molecular and Cellular Biochemistry, College of Medicine, University of Kentucky, Lexington, KY 40536.|Center for Pharmaceutical Research and Innovation, College of Pharmacy, University of Kentucky, Lexington, KY 40536.
authors.forename: Vitaliy M
authors.initials: VM
authors.lastname: Sviripa
authors.affiliation: Graduate Center for Toxicology, College of Medicine, University of Kentucky, Lexington, KY 40536.
authors.forename: Nikhil
authors.initials: N
authors.lastname: Hebbar
authors.affiliation: Department of Molecular and Cellular Biochemistry, College of Medicine, University of Kentucky, Lexington, KY 40536.|Lucille Parker Markey Cancer Center, University of Kentucky, Lexington, KY 40536.
authors.forename: Wen
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Chemistry, College of Arts and Sciences, University of Kentucky, Lexington, KY 40536.
authors.forename: W John
authors.initials: WJ
authors.lastname: Layton
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536.
authors.forename: Adel
authors.initials: A
authors.lastname: Hamza
authors.affiliation: Center for Pharmaceutical Research and Innovation, College of Pharmacy, University of Kentucky, Lexington, KY 40536.|Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536.|Molecular Modeling and Biopharmaceutical Center, College of Pharmacy, University of Kentucky, Lexington, KY 40536.
authors.forename: Chang-Guo
authors.initials: CG
authors.lastname: Zhan
authors.affiliation: Department of Molecular and Cellular Biochemistry, College of Medicine, University of Kentucky, Lexington, KY 40536.|Center for Pharmaceutical Research and Innovation, College of Pharmacy, University of Kentucky, Lexington, KY 40536.|Lucille Parker Markey Cancer Center, University of Kentucky, Lexington, KY 40536.|Department of Chemistry, College of Arts and Sciences, University of Kentucky, Lexington, KY 40536.
authors.forename: David S
authors.initials: DS
authors.lastname: Watt
authors.affiliation: Department of Molecular and Cellular Biochemistry, College of Medicine, University of Kentucky, Lexington, KY 40536.|Lucille Parker Markey Cancer Center, University of Kentucky, Lexington, KY 40536.
authors.forename: Chunming
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Radiation Medicine, College of Medicine, University of Kentucky, Lexington, KY 40536.|Graduate Center for Toxicology, College of Medicine, University of Kentucky, Lexington, KY 40536.|Lucille Parker Markey Cancer Center, University of Kentucky, Lexington, KY 40536.
authors.forename: Vivek M
authors.initials: VM
authors.lastname: Rangnekar
mesh_terms: D000634:Aminoquinolines / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D009369:Neoplasms / Q000473:pathology*; D019899:Paracrine Communication / Q000187:drug effects; D014746:Vimentin / Q000037:antagonists & inhibitors* / Q000737:chemistry
chemical_list: D000634:Aminoquinolines; D051017:Apoptosis Regulatory Proteins; C000595186:Arylquin 1; D014746:Vimentin; C101296:prostate apoptosis response-4 protein