Induction of polyploidy by histone deacetylase inhibitor: A pathway for antitumor effects Journal Article

  


Authors: Xu, W. S.; Perez, G.; Ngo, L.; Gui, C. Y.; Marks, P. A.
Article Title: Induction of polyploidy by histone deacetylase inhibitor: A pathway for antitumor effects
Abstract: Histone deacetylase (HDAC) inhibitors can induce various transformed cells to undergo growth arrest and/or death. Suberoylanilide hydroxamic acid (SAHA) is an HDAC inhibitor which is in phase I/II clinical trials and has shown antitumor activity in hematologic and solid tumors at doses well tolerated by patients. HDAC is the target for SAHA, but the mechanisms of the consequent induced death of transformed cells are not completely understood. In this study, we report that SAHA induced polyploidy in human colon cancer cell line HCT116 and human breast cancer cell lines, MCF-7, MDA-MB-231, and MBA-MD-468, but not in normal human embryonic fibroblast SW-38 and normal mouse embryonic fibroblasts. The polyploid cells lost the capacity for proliferation and committed to senescence. The induction of polyploidy was more marked in HCT116 p21 WAF1-/- or HCT116 p53-/- cells than in wild-type HCT116. The development of senescence of SAHA-induced polyploidy cells was similar in all colon cell lines. The present findings indicate that the HDAC inhibitor could exert antitumor effects by inducing polyploidy, and this effect is more marked in transformed cells with nonfunctioning p21 WAF1 or p53 genes. ©2005 American Association for Cancer Research.
Keywords: controlled study; human cell; histone deacetylase inhibitor; drug activity; drug tolerability; dose response; antineoplastic agents; drug targeting; dna replication; cell proliferation; cell death; breast cancer; cell growth; embryo; colonic neoplasms; hct116 cells; antineoplastic activity; cancer cell culture; drug effect; wild type; protein p53; drug mechanism; enzyme inhibitors; cell transformation; colon cancer; cell growth processes; vorinostat; hydroxamic acids; fibroblast; senescence; cell strain mcf 7; histone deacetylases; polyploidy; concentration response; histone deacetylase; cell strain hct116; cyclin dependent kinase inhibitor 1
Journal Title: Cancer Research
Volume: 65
Issue: 17
ISSN: 0008-5472
Publisher: American Association for Cancer Research  
Date Published: 2005-09-01
Start Page: 7832
End Page: 7839
Language: English
DOI: 10.1158/0008-5472.can-04-4608
PUBMED: 16140952
PROVIDER: scopus
DOI/URL:

http://www.scopus.com/inward/record.url?eid=2-s2.0-24744434639&partnerID=40&md5=5cf1855d9cefc5970cc026074ad73aa1
Notes: --- - "Cited By (since 1996): 60" - "Export Date: 24 October 2012" - "CODEN: CNREA" - "Source: Scopus"
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MSK Authors
  1. Chang-Yun Gui
    4 Gui
  2. Weisheng Xu
    13 Xu
  3. Lang Ngo
    27 Ngo
  4. Gisela Venta-Perez
    23 Venta-Perez
  5. Paul Marks
    186 Marks
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