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
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Aminoquinolines / administration & dosage
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Aminoquinolines / chemistry
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Aminoquinolines / pharmacology*
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Animals
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Apoptosis / drug effects*
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Apoptosis Regulatory Proteins / metabolism*
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Cells, Cultured
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Humans
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Mice
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Mice, Inbred C57BL
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Molecular Structure
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Neoplasms / pathology*
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Paracrine Communication / drug effects
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Vimentin / antagonists & inhibitors*
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Vimentin / chemistry
Substances
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Aminoquinolines
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Apoptosis Regulatory Proteins
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Arylquin 1
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Vimentin
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prostate apoptosis response-4 protein
Associated data
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PubChem-Substance/199994745
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PubChem-Substance/199994746
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PubChem-Substance/199994747
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PubChem-Substance/199994748
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PubChem-Substance/199994749
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PubChem-Substance/199994750
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PubChem-Substance/199994751
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PubChem-Substance/199994752
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PubChem-Substance/199994753