Identification of Aneuploidy-Selective Antiproliferation Compounds
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Author(s)
Tang, Yun-Chi
Williams, Bret R.
Siegel, Jake J.
Amon, Angelika B
Date Issued
February 2011
Journal
Cell
Publisher
Elsevier B.V.
Citation
Tang, Yun-Chi, Bret R. Williams, Jake J. Siegel, and Angelika Amon. “Identification of Aneuploidy-Selective Antiproliferation Compounds.” Cell 144, no. 4 (February 2011): 499-512.
Version
Final published version
Abstract
Aneuploidy, an incorrect chromosome number, is a hallmark of cancer. Compounds that cause lethality in aneuploid, but not euploid, cells could therefore provide new cancer therapies. We have identified the energy stress-inducing agent AICAR, the protein folding inhibitor 17-AAG, and the autophagy inhibitor chloroquine as exhibiting this property. AICAR induces p53-mediated apoptosis in primary mouse embryonic fibroblasts (MEFs) trisomic for chromosome 1, 13, 16, or 19. AICAR and 17-AAG, especially when combined, also show efficacy against aneuploid human cancer cell lines. Our results suggest that compounds that interfere with pathways that are essential for the survival of aneuploid cells could serve as a new treatment strategy against a broad spectrum of human tumors.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Koch Institute for Integrative Cancer Research at MIT
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1016/j.cell.2011.01.017
