A decrease in cyclin B1 levels leads to polyploidization in DNA damage-induced senescence.
Adriamycin, an anthracycline antibiotic, has been used for the treatment of various types of tumours. Adriamycin induces at least two distinct types of growth repression, such as senescence and apoptosis, in a concentration-dependent manner. Cellular senescence is a condition in which cells are unable to proliferate further, and senescent cells frequently show polyploidy. Although abrogation of cell division is thought to correlate with polyploidization, the mechanisms underlying induction of polyploidization in senescent cells are largely unclear. We wished, therefore, to explore the role of cyclin B1 level in polyploidization of Adriamycin-induced senescent cells. A subcytotoxic concentration of Adriamycin induced polyploid cells having the features of senescence, such as flattened and enlarged cell shape and activated beta-galactosidase activity. In DNA damage-induced senescent cells, the levels of cyclin B1 were transiently increased and subsequently decreased. The decrease in cyclin B1 levels occurred in G2 cells during polyploidization upon treatment with a subcytotoxic concentration of Adriamycin. In contrast, neither polyploidy nor a decrease in cyclin B1 levels was induced by treatment with a cytotoxic concentration of Adriamycin. These results suggest that a decrease in cyclin B1 levels is induced by DNA damage, resulting in polyploidization in DNA damage-induced senescence.
Kikuchi
Ikue
I
Department of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 2608675, Japan.
Nakayama
Yuji
Y
Morinaga
Takao
T
Fukumoto
Yasunori
Y
Yamaguchi
Naoto
N
D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D016922:Cellular Senescence / Q000187:drug effects*; D056744:Cyclin B1 / Q000378:metabolism*; D004249:DNA Damage; D004317:Doxorubicin / Q000633:toxicity*; D006367:HeLa Cells; D006801:Humans; D011123:Polyploidy; D001616:beta-Galactosidase / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D056744:Cyclin B1; D004317:Doxorubicin; D001616:beta-Galactosidase