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

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

doi:10.1038/nchembio.1631

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

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

Research output: Contribution to journal › Article › peer-review

51 Scopus citations

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.

Original language	English
Pages (from-to)	924-926
Number of pages	3
Journal	Nature Chemical Biology
Volume	10
Issue number	11
DOIs	https://doi.org/10.1038/nchembio.1631
State	Published - Nov 1 2014

Bibliographical note

Funding 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.).

Publisher Copyright:
© 2014 Nature America, Inc. All rights reserved.

ASJC Scopus subject areas

Molecular Biology
Cell Biology

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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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AU - Hebbar, Nikhil

AU - Zhang, Wen

AU - Layton, W. John

AU - Hamza, Adel

AU - Zhan, Chang Guo

AU - Watt, David S.

AU - Liu, Chunming

AU - Rangnekar, Vivek M.

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PY - 2014/11/1

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N2 - 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.

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

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Bibliographical note

ASJC Scopus subject areas

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