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Cell Biology International (2010) 34, 645–653 (Printed in Great Britain)
A decrease in cyclin B1 levels leads to polyploidization in DNA damage-induced senescence
Ikue Kikuchi, Yuji Nakayama1, Takao Morinaga, Yasunori Fukumoto and Naoto Yamaguchi1
Department of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 2608675, Japan

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 β-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.

Key words: Adriamycin, cyclin B1, fluorescein-β-d-galactopyranoside, polyploidy, senescence; β-galactosidase

Abbreviations: FBS, fetal bovine serum, FDG, fluorescein-β-d-galactopyranoside, HRP, horseradish peroxidase, SA-β-gal, senescence-associated β-galactosidase, X-gal, 5-bromo-4-chloro-3-indolyl-β-d-galactopyranoside

1Correspondence may be addressed to either of these authors (email or

Received 9 November 2009/26 February 2010; accepted 11 March 2010

Published as Cell Biology International Immediate Publication 11 March 2010, doi:10.1042/CBI20090398

© The Author(s) Journal compilation © 2010 Portland Press Limited

ISSN Print: 1065-6995
ISSN Electronic: 1095-8355
Published by Portland Press Limited on behalf of the International Federation for Cell Biology (IFCB)