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The effects of a telomere destabilizing agent on cancer cell-cycle dynamics-Integrated modelling and experiments.
MedLine Citation:
PMID:  22108242     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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 G(2)/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.
Authors:
Bartholomäus V Hirt; Jonathan A D Wattis; Simon P Preston; Charles A Laughton
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-11-18
Journal Detail:
Title:  Journal of theoretical biology     Volume:  -     ISSN:  1095-8541     ISO Abbreviation:  -     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-11-23     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0376342     Medline TA:  J Theor Biol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 Elsevier Ltd. All rights reserved.
Affiliation:
School of Mathematical Sciences, University of Nottingham, University Park, Nottingham NG7 2RD, United Kingdom.
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