Methotrexate-induced senescence in human adenocarcinoma cells is accompanied by induction of p21(waf1/cip1) expression and lack of polyploidy

Human colorectal adenocarcinoma C85 cells, treated with high dose methotrexate (1 microM; IC(50)=51 nM), undergo accelerated senescence, as the cells (i) are growth arrested at the G(1) and S phases of the cell cycle, (ii) are SA-beta-galactosidase-positive, (iii) show induced expression of p21(waf1...

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Bibliographic Details
Published in:Cancer letters 2009-10, Vol.284 (1), p.95
Main Authors: Dabrowska, Magdalena, Mosieniak, Grazyna, Skierski, Janusz, Sikora, Ewa, Rode, Wojciech
Format: Article
Language:English
Subjects:
Antimetabolites, Antineoplastic - pharmacology
Cell Cycle - drug effects
Cell Cycle - physiology
Cell Line, Tumor
Cell Survival - drug effects
Cell Survival - physiology
Cellular Senescence
Cyclin-Dependent Kinase Inhibitor p16 - metabolism
Cyclin-Dependent Kinase Inhibitor p21 - metabolism
Humans
Methotrexate - pharmacology
Polyploidy
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Summary:Human colorectal adenocarcinoma C85 cells, treated with high dose methotrexate (1 microM; IC(50)=51 nM), undergo accelerated senescence, as the cells (i) are growth arrested at the G(1) and S phases of the cell cycle, (ii) are SA-beta-galactosidase-positive, (iii) show induced expression of p21(waf1/cip1) and decreased expression of p16(INK4a), and (iv) show DNA synthesis continued at the reduced level. The fraction of C85 cells with DNA content higher than 4N is maintained at the same level (14%) in cells untreated, as well as regrown after the treatment. Multinucleation is found as the main karyotypic abnormality.
ISSN:1872-7980
DOI:10.1016/j.canlet.2009.04.015