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/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.
Dabrowska
Magdalena
M
Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur St., Warsaw 02-093, Poland. m.dabrowska@nencki.gov.pl
Mosieniak
Grazyna
G
Skierski
Janusz
J
Sikora
Ewa
E
Rode
Wojciech
W
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D016922:Cellular Senescence; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D006801:Humans; D008727:Methotrexate / Q000494:pharmacology*; D011123:Polyploidy
D000964:Antimetabolites, Antineoplastic; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D008727:Methotrexate