Abstract
Taxanes are an important new class of anticancer agents that inhibit
cell division by the unique mechanism of increasing the rate of
microtubule assembly and preventing microtubule depolymerisation. Using
the colony inhibition assay, we compared the cytotoxicity of paclitaxel
and docetaxel in three human neuroblastoma (NB) cell lines, SH-SY5Y,
BE(2)M17 and CHP100. Different exposure times (3, 6, 12, 24, 48 and 72
h) and different concentrations ranging from 0.1 nM to 10 mu M were
tested. Both paclitaxel and docetaxel show antineoplastic activity in
human NE cell lines. Taxanes' antitumour activity varied among the
different cell lines, CHP100 being the most sensitive and SH-SY5Y the
least sensitive. Paclitaxel cytotoxicity appears schedule-dependent,
with marked cell kill observed only for exposures of 24 h or longer.
Docetaxel cytotoxicity was dependent upon prolonged exposure only in the
SH-SY5Y cell line, while an exposure time of 3-6 h resulted in
exponential cell kill in the other two cell. lines. Docetaxel was more
cytotoxic than paclitaxel with a mean ratio of (paclitaxel/docetaxel)
IC50 values ranging from 2 to 11. For both taxanes, we observed good
correlation between cytotoxic effect and percentage of cells blocked in
G2/M phase. A cytotoxic effect occurred at concentrations comparable
with those achieved in the plasma of patients treated with these agents
in initial clinical trials. The full potential of prolonged infusion or
repeated daily administrations of taxanes should be explored in clinical
studies, and responses to taxanes in neuroblastoma should be assessed in
paediatric phase II studies.
Lingua originale | English |
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pagine (da-a) | 494-499 |
Numero di pagine | 6 |
Rivista | European Journal of Cancer |
Volume | 31A |
DOI | |
Stato di pubblicazione | Pubblicato - 1995 |
Keywords
- CYTOTOXICITY
- DOCETAXEL
- NEUROBLASTOMA
- PACLITAXEL