The NMDA antagonist dizocilpine (A) and the AMPA
antagonist GYKI52466 (B) exert concentration-dependent
antiproliferative effect in human tumor cell lines but not in human
skin fibroblasts and bone marrow stromal cells. Cells were exposed to
either culture medium alone (control), dizocilpine (1–250 μM), or
GYKI52466 (1–250 μM) for 96 h, and viability was measured
photometrically by means of the MTT assay. Data represent mean
normalized optical densities ± SEM of 6–8 trials and were
analyzed by means of linear regression. (C) Growth
inhibition of neuroblastoma cells in three-dimensional cultures by
dizocilpine (100–500 μM) is shown. Numbers of cells were assessed by
counting, after trypsinization. ANOVA showed that the effect of
treatment was significant [F(3,36) = 49.33, P
< 0.001], with multiple comparisons revealing that dizocilpine
induced antiproliferative action in a dose-dependent manner. The effect
of time was also significant [F(4,36) = 296.69,
P < 0.001], indicating that the antiproliferative
effect of dizocilpine was more pronounced with time. SKNAS, human
neuroblastoma; TE671, human rhabdomyosarcoma/medulloblastoma;
MOGGCCM, human brain astrocytoma; FTC238, human thyroid carcinoma;
A549, human Caucasian lung carcinoma; LS180, human Caucasian colon
adenocarcinoma; T47D, human breast carcinoma; HT29, human colon
adenocarcinoma; HSF, human skin fibroblasts; BMSC, human bone marrow
stromal cells.