To study the effect of harmine on the morphology of NB cells, four NB cell lines were exposed to 100 μM harmine. As early as 24 h after treatment, the plated cells began to show signs of morphological changes associated with apoptosis (Additional file
1: Fig. S1). In comparison to control cells, treated cells were smaller in size, rounded in shape, and more detached from the plate surface. After 72 h, the majority of treated cells had become spherical in shape and had detached (Fig.
2a). To determine if harmine induces dose- and time-dependent cell death, the four NB cell lines were treated with increasing drug concentrations (0, 6, 12.5, 25, 50, and 100 μM) and cell viability was measured after 24, 48 or 72 h of treatment (Fig.
2b). Increased treatment length with harmine caused decreased IC
50 in all four cell lines. The IC
50 values for SKNBE, KELLY, and SKNFI after a 72 h treatment of harmine were 169.6 ± 0.10, 170.8 ± 0.10, and 791.7 ± 0.77 μM, respectively. The IC
50 value of SKNAS after 72 h could not be calculated (for all IC
50 values including 24 and 48 h time points; see Additional file
1: Table S1). The IC
50 decrease was consistent with the morphological changes observed in the treated cells (Fig.
2a). Moreover, the IC
50 values suggest that harmine is more toxic to
MYCN-amplified NB cell lines (SKNBE and KELLY), than to NB cell lines with a normal
MYCN gene copy number (SKNAS and SKNFI).