Abstract
Background: Paclitaxel (Taxol) is known to act mainly in mitosis, interfering with microtubule dynamics, but effects on the other cells cycle phases have been reported also. However, a comparative picture of perturbation and killing in the G1, S and G2M phases after drug treatment is lacking. The approach developed by our group tackles the problem of the complexity of cell cycle effects with the aid of a computer program simulating cell cycle progression and new quantities measuring cell-cycle arrest and death. Methods: The program generates data that were compared with those given by absolute cell counts and by different flow cytometry techniques, enabling us to follow the fate of G1 and G2M blocked cells either re-entering the cycle or dying, distinguishing cytostatic and cytotoxic effects. Apoptosis was analyzed in order to refine the description of cytotoxic effects. Results: We estimated the number of blocked and dead cells after short-term Taxol treatments in a range of concentrations and post-drug incubation times. G2M block was immediately active at low concentrations but was reversible, becoming irreversible only at the highest concentrations. G1 block became active later, allowing cell cycle progression of cells initially in G1, but was still active 48 h post- treatment, at intermediate concentrations. S-phase delay was detected after 24 h. The death rate was much higher within G1 than G2M blocked cells. Conclusions: Our analysis unraveled the complexity of cell cycle effects of the drug, and revealed the activity of G1 checkpoint, hidden by a prompter but less cytotoxic G2M block.
| Original language | English |
|---|---|
| Pages (from-to) | 113-124 |
| Number of pages | 12 |
| Journal | Cytometry |
| Volume | 37 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Oct 1 1999 |
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Keywords
- Apoptosis
- Cell cycle
- Cell proliferation
- Chemotherapy
- Flow cytometry
- Mathematical models
- Taxol
ASJC Scopus subject areas
- Hematology
- Cell Biology
- Pathology and Forensic Medicine
- Biophysics
- Endocrinology
Cite this
Measuring the complexity of cell cycle arrest and killing of drugs : Kinetics of phase-specific effects induced by taxol. / Sena, Giovanni; Onado, Carlo; Cappella, Paolo; Montalenti, Francesco; Ubezio, Paolo.
In: Cytometry, Vol. 37, No. 2, 01.10.1999, p. 113-124.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Measuring the complexity of cell cycle arrest and killing of drugs
T2 - Kinetics of phase-specific effects induced by taxol
AU - Sena, Giovanni
AU - Onado, Carlo
AU - Cappella, Paolo
AU - Montalenti, Francesco
AU - Ubezio, Paolo
PY - 1999/10/1
Y1 - 1999/10/1
N2 - Background: Paclitaxel (Taxol) is known to act mainly in mitosis, interfering with microtubule dynamics, but effects on the other cells cycle phases have been reported also. However, a comparative picture of perturbation and killing in the G1, S and G2M phases after drug treatment is lacking. The approach developed by our group tackles the problem of the complexity of cell cycle effects with the aid of a computer program simulating cell cycle progression and new quantities measuring cell-cycle arrest and death. Methods: The program generates data that were compared with those given by absolute cell counts and by different flow cytometry techniques, enabling us to follow the fate of G1 and G2M blocked cells either re-entering the cycle or dying, distinguishing cytostatic and cytotoxic effects. Apoptosis was analyzed in order to refine the description of cytotoxic effects. Results: We estimated the number of blocked and dead cells after short-term Taxol treatments in a range of concentrations and post-drug incubation times. G2M block was immediately active at low concentrations but was reversible, becoming irreversible only at the highest concentrations. G1 block became active later, allowing cell cycle progression of cells initially in G1, but was still active 48 h post- treatment, at intermediate concentrations. S-phase delay was detected after 24 h. The death rate was much higher within G1 than G2M blocked cells. Conclusions: Our analysis unraveled the complexity of cell cycle effects of the drug, and revealed the activity of G1 checkpoint, hidden by a prompter but less cytotoxic G2M block.
AB - Background: Paclitaxel (Taxol) is known to act mainly in mitosis, interfering with microtubule dynamics, but effects on the other cells cycle phases have been reported also. However, a comparative picture of perturbation and killing in the G1, S and G2M phases after drug treatment is lacking. The approach developed by our group tackles the problem of the complexity of cell cycle effects with the aid of a computer program simulating cell cycle progression and new quantities measuring cell-cycle arrest and death. Methods: The program generates data that were compared with those given by absolute cell counts and by different flow cytometry techniques, enabling us to follow the fate of G1 and G2M blocked cells either re-entering the cycle or dying, distinguishing cytostatic and cytotoxic effects. Apoptosis was analyzed in order to refine the description of cytotoxic effects. Results: We estimated the number of blocked and dead cells after short-term Taxol treatments in a range of concentrations and post-drug incubation times. G2M block was immediately active at low concentrations but was reversible, becoming irreversible only at the highest concentrations. G1 block became active later, allowing cell cycle progression of cells initially in G1, but was still active 48 h post- treatment, at intermediate concentrations. S-phase delay was detected after 24 h. The death rate was much higher within G1 than G2M blocked cells. Conclusions: Our analysis unraveled the complexity of cell cycle effects of the drug, and revealed the activity of G1 checkpoint, hidden by a prompter but less cytotoxic G2M block.
KW - Apoptosis
KW - Cell cycle
KW - Cell proliferation
KW - Chemotherapy
KW - Flow cytometry
KW - Mathematical models
KW - Taxol
UR - http://www.scopus.com/inward/record.url?scp=0033215008&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033215008&partnerID=8YFLogxK
U2 - 10.1002/(SICI)1097-0320(19991001)37:2<113::AID-CYTO4>3.0.CO;2-M
DO - 10.1002/(SICI)1097-0320(19991001)37:2<113::AID-CYTO4>3.0.CO;2-M
M3 - Article
VL - 37
SP - 113
EP - 124
JO - Cytometry Part B - Clinical Cytometry
JF - Cytometry Part B - Clinical Cytometry
SN - 1552-4949
IS - 2
ER -