Document Detail

Identification of aneuploidy-selective antiproliferation compounds.
MedLine Citation:
PMID:  21315436     Owner:  NLM     Status:  MEDLINE    
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.
Yun-Chi Tang; Bret R Williams; Jake J Siegel; Angelika Amon
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cell     Volume:  144     ISSN:  1097-4172     ISO Abbreviation:  Cell     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-02-21     Completed Date:  2011-03-31     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  0413066     Medline TA:  Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  499-512     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier Inc. All rights reserved.
David H. Koch Institute for Integrative Cancer Research, Cambridge, MA 02139, USA.
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MeSH Terms
Aminoimidazole Carboxamide / analogs & derivatives,  pharmacology
Antineoplastic Agents / isolation & purification*,  pharmacology
Benzoquinones / pharmacology
Cell Line
Cell Proliferation / drug effects
Chloroquine / pharmacology
Chromosome Segregation
Drug Screening Assays, Antitumor*
Embryo, Mammalian / cytology
Fibroblasts / drug effects
Lactams, Macrocyclic / pharmacology
Neoplasms / drug therapy,  genetics*
Ribonucleotides / pharmacology
Grant Support
//Howard Hughes Medical Institute; //Howard Hughes Medical Institute
Reg. No./Substance:
0/Antineoplastic Agents; 0/Benzoquinones; 0/Lactams, Macrocyclic; 0/Ribonucleotides; 360-97-4/Aminoimidazole Carboxamide; 4GY0AVT3L4/tanespimycin; 54-05-7/Chloroquine; F0X88YW0YK/AICA ribonucleotide
Comment In:
Cell. 2011 Feb 18;144(4):465-6   [PMID:  21335229 ]
Nat Rev Cancer. 2011 Apr;11(4):231   [PMID:  21548394 ]
Nat Rev Drug Discov. 2011 Apr;10(4):258   [PMID:  21455233 ]

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