| Induction of senescence with doxorubicin leads to increased genomic instability of HCT116 cells. | |
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MedLine Citation:
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PMID: 18538372 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Induction of senescence has been proposed as a possible in vivo tumor response to anticancer treatment. Senescent cancer cells are often polyploid, however, their route to polyploidy is poorly recognized (endoreduplication versus aberrant mitoses). We showed that after treatment of HCT116 cells with a low dose of doxorubicin most of them stopped proliferation as documented by SA-beta-galactosidase activity and the lack of Ki67 expression. Increased expression of other common senescence markers, p53, p21 and cyclin D1, was also observed. The cells became giant, polyploid and polymorphic, with multinucleated cells comprising a substantial fraction. The vast majority of the doxorubicin-treated cells did not enter mitoses, as evidenced by mitotic index analysis, as well as by the predominantly cytoplasmic localization of cyclin B1 and a lack of separation of multiplied centrosomes. This allowed us to conclude that doxorubicin-treated HCT116 cells underwent endoreduplication. However, the rare events of aberrant mitoses of polyploid cells observed by us led to aneuploid progeny as was documented by cytogenetic analysis of survivors. Thus, a senescence-inducing treatment of HCT116 cancer cells had a dual effect-it stopped the proliferation of the majority of the cells, but also led to the appearance of proliferating aneuploid ones. |
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Authors:
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Malgorzata A Sliwinska; Grazyna Mosieniak; Kamila Wolanin; Aneta Babik; Katarzyna Piwocka; Adriana Magalska; Joanna Szczepanowska; Jan Fronk; Ewa Sikora |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2008-05-01 |
Journal Detail:
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Title: Mechanisms of ageing and development Volume: 130 ISSN: 0047-6374 ISO Abbreviation: Mech. Ageing Dev. Publication Date: 2009 Jan-Feb |
Date Detail:
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Created Date: 2009-01-19 Completed Date: 2009-04-13 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0347227 Medline TA: Mech Ageing Dev Country: Ireland |
Other Details:
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Languages: eng Pagination: 24-32 Citation Subset: IM |
Affiliation:
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Department of Biochemistry, Nencki Institute of Experimental Biology, Pasteura 3, 02-093 Warsaw, Poland. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antibiotics, Antineoplastic
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pharmacology* Apoptosis / drug effects Cell Aging / drug effects* Colonic Neoplasms / drug therapy*, genetics*, pathology DNA Replication / drug effects Disease Progression Doxorubicin / pharmacology* Genomic Instability / drug effects* HCT116 Cells Humans Mitosis / drug effects Polyploidy |
| Chemical | |
Reg. No./Substance:
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0/Antibiotics, Antineoplastic; 23214-92-8/Doxorubicin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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