A Checkpoint-oriented cell cycle simulation model

International audienceModeling and in silico simulations are of major conceptual and applicative interest for studying the cell cycle and proliferation in eukaryotic cells. In this paper, we present a cell cycle checkpoint-oriented simulator that uses agent-based simulation modeling to reproduce the dynamics of a cancer cell population in exponential growth. Our in silico simulations were successfully validated by experimental in vitro supporting data obtained with HCT116 colon cancer cells. We demonstrated that this model can simulate cell confluence and the associated elongation of the G1 phase. Using nocodazole to synchronize cancer cells at mitosis, we confirmed the model predictivity, and provided evidence of an additional and unexpected effect of nocodazole on the overall cell cycle progression. We anticipate that this cell cycle simulator will be a potential source of new insights and research perspectives

Optimization of synchronization experiments using a checkpoint-oriented cell cycle simulator

National audienceCell cycle synchronization at a specific stage is often an essential requirement to investigate biological events and mechanisms using the large panel of molecular and cellular biology technologies. Optimization of the synchronization parameters is most of the time neglected, which could result in experimental time wasting or even in erroneous conclusions. Here we report the development of a cell cycle checkpoint-oriented simulator, based on agent-based modeling (ABM), that reproduces the dynamic behavior of a proliferating cell population and its response to checkpoint activation

Design, synthesis, and biological evaluation of novel naphthoquinone derivatives with CDC25 phosphatase inhibitory activity.

CDC25 dual-specificity phosphatases are essential key regulators of eukaryotic cell cycle progression and the CDC25A and B isoforms are over-expressed in different tumors and related cancer cell lines. CDC25s are now considered to be interesting targets in the search for novel anticancer agents. We describe new compounds derived from vitamin K3 that inhibit CDC25B activity with IC50 values in the low micromolar range. These naphthoquinone derivatives also display antiproliferative activity on HeLa cells as expected for CDC25 inhibitors and inhibit cell growth in a clonogenic assay at submicromolar concentrations. They increase inhibitory tyrosine 15 phosphorylation of CDK and induce the cleavage of PARP, a hallmark of apoptosis