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

56 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

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

Funding

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.).

Funders	Funder number
University of Kentucky Center for Clinical and Translational Science Drug Discovery Pilot
National Institutes of Health (NIH)
National Childhood Cancer Registry – National Cancer Institute	R21 CA179283, R01 CA60872
National Childhood Cancer Registry – National Cancer Institute
National Center for Research Resources	P20RR020171
National Center for Research Resources

ASJC Scopus subject areas

Molecular Biology
Cell Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Cite this

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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 - Zhan, Chang Guo

AU - Watt, David S.

AU - Liu, Chunming

AU - Rangnekar, Vivek M.

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

Abstract

Bibliographical note

Funding

ASJC Scopus subject areas

UN SDGs

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