Abstract
We previously reported that mitotic catastrophe (MC) is involved in induction of senescence-like growth arrest (SLGA) in tumor cells. Since imperfect persistence of G2 checkpoint allows cells to progress to mitosis, the question arises how irreversible growth arrest is induced in tumor cells undergoing MC. We here analyze cell cycle during SLGA-induction in MCF-7 transfected FUCCI-system, by which cell cycle phase is visualized by live-cell imaging.
Live-cell imaging observation revealed that G1-irradiation induced MC in 40 % of cells in which the majority passed through G1 within an average of 6 hr post-irradiation, indicating that irradiation of G1 cells after restriction point allowed induction of MC. The other 60 % of non-dividing population persisted in G1 via either prolonged G1 from immediately after irradiation or transition into next G1 after rounding of cell cycle followed by bypass of mitosis. In case of G2-irradiation, it was also found induction of MC with nearly the same frequency as that by G1-irradiation. MC was induced in cells released from transient G2 arrest, or in cells that bypassed mitosis and rounded cell cycle, in turn, entered mitosis. Regardless of the pathway passed through post-irradiation, cells underwent MC eventually persisted in G1. Interestingly, all non-dividing cells irradiated at G2 bypassed mitosis and persisted in next G1. Taken together, our results indicate that the mechanism to sustain cell cycle in G1 plays a quite important function in the induction of SLGA in MCF-7.
