کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
8285333 1535659 2009 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Induction of senescence with doxorubicin leads to increased genomic instability of HCT116 cells
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی سالمندی
پیش نمایش صفحه اول مقاله
Induction of senescence with doxorubicin leads to increased genomic instability of HCT116 cells
چکیده انگلیسی
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-β-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.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Mechanisms of Ageing and Development - Volume 130, Issues 1–2, January–February 2009, Pages 24-32
نویسندگان
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