Cancer cell dynamics in presence of telomerase inhibitors: analysis of in vitro data.
The inhibition of telomerase activity in actively dividing cells leads to suppression of cell growth after a time delay (inhibitory delay) required to reach a threshold telomeric DNA size. We developed a mathematical model of the dynamics of telomere size distribution and cell growth in the presence of telomere inhibitors that allowed quantification of the inhibitory delay. The model based on the solution of a system of differential equations described quantitatively recent experimental data on dynamics of cultured cells in presence of telomerase inhibitors. The analysis of the data by this model suggested the existence of at least two distinct subpopulations of cells with different proliferative activity. Size distribution of telomeres, fraction of proliferating cells, and tumor doubling times are of critical importance for the dynamics of cancer cells growth in presence of telomerase inhibitors. Rapidly growing cells with large telomeric DNA heterogeneity and small proliferating fractions as well as those with very short homogeneous telomeres would be the most sensitive to telomerase inhibitors.
Sidorov
Igor A
IA
National Cancer Institute, NIH, Bldg. 469, PO Box B, Frederick, MD 21702, USA.
Hirsch
Ken S
KS
Harley
Calvin B
CB
Dimitrov
Dimiter S
DS
D016923:Cell Death; D002455:Cell Division; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006801:Humans; D008957:Models, Genetic; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D019098:Telomerase / Q000037:antagonists & inhibitors*; D016615:Telomere / Q000502:physiology* / Q000648:ultrastructure; D013997:Time Factors
D004791:Enzyme Inhibitors; D019098:Telomerase