ICRF-193, a catalytic inhibitor of DNA topoisomerase II, delays the cell cycle progression from metaphase, but not from anaphase to the G1 phase in mammalian cells.
We have shown previously that ICRF-193, a catalytic inhibitor of DNA topoisomerase II (topo II), delays cell cycle progression in HeLa S3 cells. We report here that the delay of the transition in M phase is observed when HeLa S3 cells were treated with ICRF-193 during metaphase, but not thereafter. ICRF-193 also delayed the degradation of cyclin B in the transition from M to G1 phase, while in Chinese hamster ovary (CHO) cells the drug did not delay the progression in M phase. Since HeLa S3 and CHO cells are 'stringent' and 'relaxed' in mitotic control, respectively, it is suggested that under topo II inhibition, the M phase checkpoint operates through an inability for chromosome segregation.
Iwai
M
M
Laboratory of Biochemistry, Aichi Cancer Center Research Institute, Chikusa-ku, Nagoya, Japan.
Hara
A
A
Andoh
T
T
Ishida
R
R
D000705:Anaphase / Q000187:drug effects; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D016213:Cyclins / Q000378:metabolism; D054659:Diketopiperazines; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016193:G1 Phase / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D008677:Metaphase / Q000187:drug effects*; D010879:Piperazines / Q000494:pharmacology*; D059005:Topoisomerase II Inhibitors
D016213:Cyclins; D054659:Diketopiperazines; D004791:Enzyme Inhibitors; D010879:Piperazines; D059005:Topoisomerase II Inhibitors; C070899:4,4'-(1,2-dimethyl-1,2-ethanediyl)bis-2,6-piperazinedione