CYTOTOXICITY OF PACLITAXEL AND DOCETAXEL IN HUMAN NEUROBLASTOMA CELL-LINES

Taxanes are an important new class of anticancer agents that inhibit c ell division by the unique mechanism of increasing the rate of microtu bule assembly and preventing microtubule depolymerisation. Using the c olony 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 teste d. Both paclitaxel and docetaxel show antineoplastic activity in human NE cell lines. Taxanes' antitumour activity varied among the differen t cell lines, CHP100 being the most sensitive and SH-SY5Y the least se nsitive. Paclitaxel cytotoxicity appears schedule-dependent, with mark ed 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 ce ll kill in the other two cell. lines. Docetaxel was more cytotoxic tha n paclitaxel with a mean ratio of (paclitaxel/docetaxel) IC50 values r anging from 2 to 11. For both taxanes, we observed good correlation be tween cytotoxic effect and percentage of cells blocked in G2/M phase. A cytotoxic effect occurred at concentrations comparable with those ac hieved 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 studie s, and responses to taxanes in neuroblastoma should be assessed in pae diatric phase II studies.