S-phase specificity of cell killing by docetaxel (Taxotere) in synchronised HeLa cells

Cell viability following short (1 h) contact with paclitaxel or docetaxel was assayed using synchronised HeLa cells. Docetaxel proved almost totally lethal against S-phase cells. Its toxicity was only partial against cells in mitosis, and declined to a minimum with progression to G1. For paclitaxel,...

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Bibliographic Details
Published in:British journal of cancer 1995-06, Vol.71 (6), p.1194-1198
Main Authors: Hennequin, C, Giocanti, N, Favaudon, V
Format: Article
Language:English
Subjects:
Antineoplastic agents
Antineoplastic Agents, Phytogenic - toxicity
Biological and medical sciences
Biological Transport
Biomedical and Life Sciences
Biomedicine
Cancer Research
Cell Cycle - drug effects
Cell Division - drug effects
Cell Survival - drug effects
Docetaxel
Drug Resistance
Epidemiology
experimental-oncology
General aspects
HeLa Cells
Humans
Kinetics
Medical sciences
Molecular Medicine
Oncology
Paclitaxel - analogs & derivatives
Paclitaxel - metabolism
Paclitaxel - toxicity
Pharmacology. Drug treatments
S Phase
Taxoids
Time Factors
Tritium
Tumor Stem Cell Assay
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Summary:Cell viability following short (1 h) contact with paclitaxel or docetaxel was assayed using synchronised HeLa cells. Docetaxel proved almost totally lethal against S-phase cells. Its toxicity was only partial against cells in mitosis, and declined to a minimum with progression to G1. For paclitaxel, cytotoxicity increased with progression through S and G2, peaked at the time of mitosis, and decreased thereafter. Maximum resistance to paclitaxel was in early S. Although lethal, brief exposure to docetaxel in S-phase did not delay progression through S and G2. Gross damage was detectable immediately after mitosis, with dysfunction in cytokinesis and accumulation of multinucleated, non-viable cells. Arrest of cells at prometaphase required continuous contact with lethal amounts of docetaxel or reintroduction of drug shortly before mitosis following pulse-chase treatment in mid-S-phase. Paclitaxel at moderate doses presumably acts mostly via damage to the mitotic spindle. In contrast, the available data suggest that docetaxel primarily targets centrosome organisation, leading to abortive mitosis and cell death.
ISSN:0007-0920
1532-1827
DOI:10.1038/bjc.1995.232