A saturation threshold for taxol cytotoxicity in human glial and neuroblastoma cells.
The cytotoxic effects of taxol at concentrations of 0.001-1.0 microgram/ml were determined in two human glioblastoma multiforme, two neuroblastoma and two primitive neuroectodermal tumor cell lines. The neuroectodermal cell lines were established from previously treated patients, while the glioblastomas were from untreated patients. At exposure durations of 1, 4 and 24 h there was an inverse taxol concentration-survival relationship for all six cell lines as measured by the MTT method. Significant differences in sensitivity to taxol among these cell lines were observed; the most resistant cell line SK-N-FI is characterized by very high levels of MDR1 expression and the most sensitive SK-N-AS by very low levels. An additional level of complexity concerns a saturation threshold for taxol-induced cytotoxic effects which when reached precludes additional effects of prolonged or additional exposure. Tumors of the brain and peripheral nervous system appear to be sensitive to taxol. However, dosage necessary to maximize cytocidal effects in tumors requires knowledge of at least the range of each tumors constitutive sensitivity to taxol and a way to optimize drug delivery.
Helson
L
L
New York Medical College, Valhalla, NY 10595.
Helson
C
C
Malik
S
S
Ainsworth
S
S
Mangiardi
J
J
D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D005909:Glioblastoma / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D009447:Neuroblastoma / Q000188:drug therapy*; D018242:Neuroectodermal Tumors, Primitive / Q000188:drug therapy; D017239:Paclitaxel / Q000493:pharmacokinetics* / Q000633:toxicity*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D017239:Paclitaxel