Jump to main content
Jump to site search

Issue 1, 2015
Previous Article Next Article

Target discovery of acivicin in cancer cells elucidates its mechanism of growth inhibition

Author affiliations

Abstract

Acivicin is a natural product with diverse biological activities. Several decades ago its clinical application in cancer treatment was explored but failed due to unacceptable toxicity. The causes behind the desired and undesired biological effects have never been elucidated and only limited information about acivicin-specific targets is available. In order to elucidate the target spectrum of acivicin in more detail we prepared functionalized derivatives and applied them for activity based proteomic profiling (ABPP) in intact cancer cells. Target deconvolution by quantitative mass spectrometry (MS) revealed a preference for specific aldehyde dehydrogenases. Further in depth target validation confirmed that acivicin inhibits ALDH4A1 activity by binding to the catalytic site. In accordance with this, downregulation of ALDH4A1 by siRNA resulted in a severe inhibition of cell growth and might thus provide an explanation for the cytotoxic effects of acivicin.

Graphical abstract: Target discovery of acivicin in cancer cells elucidates its mechanism of growth inhibition

Back to tab navigation

Supplementary files

Publication details

The article was received on 03 Aug 2014, accepted on 09 Sep 2014 and first published on 16 Sep 2014


Article type: Edge Article
DOI: 10.1039/C4SC02339K
Citation: Chem. Sci., 2015,6, 237-245
  • Open access: Creative Commons BY license
  •   Request permissions

    Target discovery of acivicin in cancer cells elucidates its mechanism of growth inhibition

    J. Kreuzer, N. C. Bach, D. Forler and S. A. Sieber, Chem. Sci., 2015, 6, 237
    DOI: 10.1039/C4SC02339K

    This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. Material from this article can be used in other publications provided that the correct acknowledgement is given with the reproduced material.

    Reproduced material should be attributed as follows:

    • For reproduction of material from NJC:
      [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the Centre National de la Recherche Scientifique (CNRS) and the RSC.
    • For reproduction of material from PCCP:
      [Original citation] - Published by the PCCP Owner Societies.
    • For reproduction of material from PPS:
      [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the European Society for Photobiology, the European Photochemistry Association, and RSC.
    • For reproduction of material from all other RSC journals:
      [Original citation] - Published by The Royal Society of Chemistry.

    Information about reproducing material from RSC articles with different licences is available on our Permission Requests page.

Search articles by author

Spotlight

Advertisements