Figure 1
Screening of a FDA-approved drug library for inducers of ADAM10 promoter activity enhancers. (a) SH-SY5Y cells were incubated for 48 h with 0.1% v/v substance and viability assessed using the Cell Titer Glo assay. DMSO (solvent) served as control and values obtained for solvent-treated cells were set to 100%. Dashed lines indicate the maximum tolerated proliferative or toxic effect. Concentrations were subsequently adjusted by further dilution until no toxic/proliferative effect could be observed. 13 substances were excluded from further analyses due to their remaining high toxic potential (for final conc. see Suppl. Table 1). (b) SH-SY5Y cells were transiently transfected with a dual reporter vector for both promoter activities, human ADAM10 and BACE-1 (20). Subsequently, cells were incubated with the respective drug or DMSO as a solvent-control (values set to 100%). The experiment was conducted three-times independently (SDs are not shown for clarity of the graph). The main part of the tested drugs remained without effects (dark grey box) while a small number of drugs revealed promoter- inducing potential (light grey box). The most promising candidate, i.e. high ADAM10 promoter activity and low BACE-1 promoter activity (disulfiram), is indicated by an arrow.
