A representative plot for synergistic drug https://www.selleckchem.com/products/fg-4592.html interaction is presented in Figure 3. Table 1 Summary of drug combinations   IC50 (μM) Cell line Oxaliplatin ± FWGE p-value 5-FU ± FWGE p-value CPT-11 ± FWGE p-value   – +   – +   – +   HCT-8 0,43 ± 0,03 0,45 ± 0,03 0,52 2,65 ± 0,35 1,2 ± 0,6 0,023*

2,0 ± 0,46 1,8 ± 0,32 0,63 HCT-15 0,95 ± 0,19 0,57 ± 0,25 0,05 4,45 ± 0,72 1,45 ± 0,61 0,0001* 4,5 ± 0,3 3,4 ± 0,31 0,001* HCT116 0,39 ± 0,06 0,19 ± 0,09 0,01* 4,6 ± 0,38 2,9 ± 0,9 0,01* 1,2 ± 0,1 0,96 ± 0,11 0,01* HT29 0,32 ± 0,09 0,35 ± 0,05 0,53 0,99 ± 0,31 1,3 ± 0,6 0,39 3,5 ± 0,3 4,1 ± 0,23 0,05 DLD-1 2,47 ± 0,17 2,2 ± 0,8 0,61 3,2 ± 0,21 1,6 ± 0,7 0,02* 6,6 ± 0,6 6,1 ± 0,85 0,43 Colo205 0,45 ± 0,05 0,24 ± 0,05 0,001* 0,54

± 0,12 0,44 ± 0,1 0,26 1,2 ± 0,19 1,1 ± 0,19 0,24 Colo320 1,1 ± 0,34 0,84 ± 0,13 0,33 1,35 ± 0,133 0,57 ± 0,03 0,001* 8,5 ± 3,4 8,7 ± 3,1 0,92 SW48 0,13 ± 0,02 0,1 ± 0,02 0,09 3,4 ± 0,2 2,2 ± 0,2 0,002* 2,4 ± 0,35 2,1 ± 0,29 0,18 SW480 0,57 ± 0,11 0,37 ± 0,12 0,06 2,7 ± 0,17 2,9 ± 1,5 0,83 6,4 ± 1,2 6,9 ± 2,3 0,72 n ≥ 3, asterisk indicates significant synergistic drug interaction Figure 3 Synergy between FWGE and 5-FU in human colon cancer cell line HCT15. Plots represent the average of 3 independent experiments. The hypothetical curve was calculated as described by Drewinko et al. [16]. Synergy is indicated by the hypothetical curve which runs above Vorinostat in vivo the combination curve. Sequential drug application of FWGE and 5-FU in the human colon cancer cell lines HT29 and HCT-8 To evaluate the influence of drug scheduling, exponentially growing cells were Small molecule library datasheet exposed to an IC30 of FWGE 24 h after seeding which was followed by serial dilutions of 5-FU after further 24 hours or vice versa. Cells were fixated after 120 h total assay time and processed according to the SRB protocol. IC50 values were calculated based on the Hill equation using Sigma plot and the data were summarized in table 2. In both cell lines, if 5-FU was followed

by FWGE, we observed an additive drug interaction. On the other hand, if FWGE precedes 5-FU for 24 hours, we observed Janus kinase (JAK) a trend to antagonism in both cell lines. However, this antagonism did not reach statistical significance. Taken together, these findings suggest that the interactions between 5-FU and FWGE are schedule-dependent. Schedules in which FWGE precedes 5-FU should be avoided. Table 2 Schedule effect of FWGE and 5-FU   IC50 (μM) Cell line 5-FU 5-FU→FWGE p-value 5-FU FWGE→5-FU p-value HCT-8 1,52 1,57 > 0.05 1,74 2,20 > 0.05 HT29 1,10 1,06 > 0.05 1,77 2,23 > 0.05 n ≥ 3; cells were exposed to either 5-FU 24 h after plating followed by FWGE after additional 24 h or vice versa up to a total assay time of 120 h.