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【bio-news】对非整倍体的识别选择性细胞增殖有抑
Identification of Aneuploidy-Selective Antiproliferation Compounds
Authors
Yun-Chi Tang, Bret R. Williams, Jake J. Siegel, Angelika Amon
Highlights
?4 trisomic MEF lines were screened for compounds that antagonize their proliferation
?The AMPK agonist AICAR and the Hsp90 inhibitor 17-AAG induce apoptosis in trisomic MEFs
?AICAR increases already elevated levels of Hsp72 and autophagy in trisomic MEFs
?AICAR+17-AAG preferentially inhibit the growth of high-grade aneuploid cancer cells
Summary
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.
http://www.cell.com/abstract/S0092-8674(11)00056-0
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作者:admin@医学,生命科学 2011-02-11 02:49
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