CYTOTOXICITY OF PACLITAXEL AND DOCETAXEL IN HUMAN NEUROBLASTOMA CELL-LINES

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