Fig. 1

IZI1551 is superior in killing melanoma cells than TRAIL or specific MAP kinase inhibitors. a Clonogenic outgrowth of mutBRAF A375 and Malme3M melanoma cells treated with dabrafenib (Dabra; 10 µM) for 8 days was compared to untreated cells (*p ≤ 0.05; ***p ≤ 0.001). b Parental and dabrafenib-conditioned melanoma cell lines A375 and Malme3M were treated with dabrafenib (Dabra; 10 µM) alone or in combination with trametinib (Trame; 1 µM). After 48 h apoptosis was determined using a Cell Death Detection ELISA (CDDE) (*p ≤ 0.05; **p ≤ 0.01; ***p ≤ 0.001; n.s. = not significant). c A375 melanoma cells were treated with increasing doses of izTRAIL or IZI1551 as indicated (ng/ml). After 24 h apoptosis was determined using a CDDE (*p ≤ 0.05; **p ≤ 0.01; ***p ≤ 0.001; n.s. = not significant). d The same dose kinetics of IZI1551 as in (c) was applied to primary human keratinocytes, fibroblasts and melanocytes. After 24 h apoptosis was determined using a CDDE (*p ≤ 0.05; ***p ≤ 0.001; n.s. = not significant). e Parental (par) and dabrafenib-conditioned (cond) melanoma cell lines A375 and Malme3M were treated with dabrafenib (Dabra; 10 µM) or IZI1551 (IZI; 50 ng/ml) alone or in combination. After 24 h of IZI1551 and 48 h of dabrafenib treatment apoptosis was determined using a CDDE (**p ≤ 0.01; ***p ≤ 0.001; n.s. = not significant) and f monitored by Western-blot analysis using antibodies against caspase-3 and PARP. α-tubulin served as loading control. For CDDE and clonogenic assay, the mean ± SD of three independently performed experiments is shown. WBs represent one out of three independently performed experiments