Cell-cycle fate-monitoring distinguishes individual chemosensitive and chemoresistant cancer cells in drug-treated heterogeneous populations demonstrated by real-time fucci imaging

Essentially every population of cancer cells or tumor is heterogeneous, especially with regard to chemosensitivity and resistance. In the present study, we utilized the fluorescent ubiquitination-based cell cycle indicator (FUCCI) imaging system to investigate the correlation between cell cycle behavior and apoptosis after treatment of cancer cells with chemotherapeutic drugs. HeLa cells expressing FUCCI were treated with doxorubicin (DOX) (5 μM) or cisplatinum (CDDP) (5 μM) for 3 h. Cell cycle progression and apoptotic changes were monitored by time-lapse FUCCI imaging for 72 h. Time-lapse FUCCI imaging demonstrated that both DOX and CDDP could induce cell cycle arrest in S/G₂/M in almost all the cells, but a subpopulation of the cells could escape the block and undergo mitosis. The subpopulation which went through mitosis subsequently underwent apoptosis while the cells arrested in S/G₂/M survived. The present results demonstrate that chemoresistant cells can be readily identified in a heterogeneous population of cancer cells by S/G₂/M arrest which can serve in future studies as a visible target for novel agents that kill cell-cycle-arrested cells.