Bartholomäus V. Hirt
The effects of a telomere destabilising agent on cancer cell-cycle dynamics - integrated modelling and experiments
Hirt, Bartholomäus V.; Wattis, Jonathan A.D.; Preston, Simon P.; Laughton, Charles A.
Jonathan A.D. Wattis Jonathan.Wattis@nottingham.ac.uk
Simon P. Preston
Charles A. Laughton
The pentacyclic acridinium salt RHPS4 displays anti-tumour properties in vitro as well as in vivo and is potentially cell-cycle specific. We have collected experimental data and formulated a compartmental model using ordinary differential equations to investigate how the compound affects cells in each stage of the cell cycle. In addition to a control case in which no drug was used, we treated colorectal cancer cells with three different concentrations of the drug and fitted simulations from our models to experimental observations. We found that RHPS4 caused a concentration-dependent, marked cell death in treated cells, which is best modelled by allowing the rate parameters corresponding to cell death to be sigmoidal functions of time. We have shown that the model is “identifiable”, meaning that, at least in principle, the parameter values can be determined from observable quantities. We find that at low concentrations RHPS4 primarily affects the cells in the G2/M phase, and that the drug has a delayed effect with the delay decreasing at larger doses. Since the drug diffuses into the nucleus, the observed delayed effect of the compound is unexpected and is a novel finding of our research into this compound.
|Journal Article Type||Article|
|Publication Date||Feb 21, 2012|
|Journal||Journal of Theoretical Biology|
|Peer Reviewed||Peer Reviewed|
|Institution Citation||Hirt, B. V., Wattis, J. A., Preston, S. P., & Laughton, C. A. (2012). The effects of a telomere destabilising agent on cancer cell-cycle dynamics - integrated modelling and experiments. Journal of Theoretical Biology, 295, doi:10.1016/j.jtbi.2011.10.038|
|Copyright Statement||Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0|
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0