Table 3.
The conversion of Lip-C6-delivered C6-ceramide to natural ceramide species is altered by Lip-PDMP alone or in combination with gemcitabine
| Ceramide (Fatty Acid) | Control | Lip-Ghost | Lip-C6 | Gem | Lip-PDMP | Lip-C6 + Gem | Lip-C6 + Lip-PDMP | Lip-PDMP + Gem | Lip-C6 + Lip-PDMP + Gem |
| C14:0 | 3.21 ± 0.24 | 2.75 ± 0.26 | 5.94 ± 0.47# | 2.80 ± 0.38 | 3.50 ± 0.09 | 6.69 ± 0.75* | 11.66 ± 1.07*$ | 3.08 ± 0.60 | 15.62 ± 0.92*,$,@ |
| C16:0 | 54.68 ± 3.17 | 39.48 ± 4.11 | 86.56 ± 5.57# | 41.80 ± 5.61 | 37.12 ± 1.79 | 111.04 ± 14.54* | 77.14 ± 5.58# | 29.54 ± 2.23 | 113.58 ± 11.99* |
| C16:1 | 0.41 ± 0.03 | 0.37 ± 0.05 | 0.73 ± 0.03* | 0.39 ± 0.04 | 0.29 ± 0.04 | 0.78 ± 0.09* | 1.01 ± 0.09* | 0.27 ± 0.04 | 1.02 ± 0.09* |
| C18:0 | 2.04 ± 0.29 | 1.62 ± 0.31 | 5.19 ± 0.38 | 1.13 ± 0.19 | 1.23 ± 0.15 | 6.23 ± 1.00# | 5.31 ± 1.10 | 1.54 ± 0.29 | 13.58 ± 1.90*,$,@ |
| C18:1 | 0.45 ± 0.04 | 0.35 ± 0.04 | 1.13 ± 0.05* | 0.36 ± 0.06 | 0.27 ± 0.01 | 1.37 ± 0.13* | 1.31 ± 0.12* | 0.24 ± 0.02 | 1.66 ± 0.07*,$ |
| C20:0 | 0.19 ± 0.04 | 0.15 ± 0.04 | 0.44 ± 0.04 | 0.09 ± 0.02 | 0.09 ± 0.01 | 0.69 ± 0.05* | 0.42 ± 0.08 | 0.16 ± 0.05 | 1.30 ± 0.15*,$,@ |
| C20:1 | 0.27 ± 0.03 | 0.22 ± 0.02 | 0.50 ± 0.04# | 0.23 ± 0.02 | 0.13 ± 0.00 | 0.62 ± 0.07* | 0.51 ± 0.09# | 0.11 ± 0.02 | 0.78 ± 0.07*,$,& |
| C22:0 | 0.44 ± 0.09 | 0.23 ± 0.03 | 0.75 ± 0.04 | 0.23 ± 0.02 | 0.24 ± 0.01 | 0.93 ± 0.15# | 1.01 ± 0.18# | 0.48 ± 0.19 | 2.60 ± 0.22*,$,@ |
| C22:1 | 1.15 ± 0.05 | 0.83 ± 0.06 | 2.98 ± 0.28# | 0.87 ± 0.10 | 0.62 ± 0.03 | 4.21 ± 0.55* | 3.57 ± 0.53* | 0.42 ± 0.07 | 6.83 ± 0.92*,$,@ |
| C24:0 | 1.15 ± 0.23 | 0.57 ± 0.05 | 1.29 ± 0.08 | 0.68 ± 0.08 | 0.59 ± 0.04 | 1.75 ± 0.28# | 1.52 ± 0.23# | 0.62 ± 0.15 | 2.25 ± 0.16*,$ |
| C24:1 | 24.76 ± 3.30 | 13.77 ± 1.35 | 29.62 ± 1.44 | 15.20 ± 2.31 | 13.15 ± 0.79 | 40.94 ± 6.70# | 30.21 ± 4.86 | 10.59 ± 1.29 | 44.91 ± 3.47* |
| C26:0 | 0.02 ± 0.01 | 0.01 ± 0.00 | 0.03 ± 0.00 | 0.01 ± 0.00 | 0.01 ± 0.00 | 0.02 ± 0.00 | 0.04 ± 0.02 | 0.02 ± 0.00 | 0.03 ± 0.01# |
| C26:1 | 0.12 ± 0.04 | 0.03 ± 0.01 | 0.10 ± 0.01 | 0.04 ± 0.00 | 0.03 ± 0.00 | 0.10 ± 0.01 | 0.12 ± 0.03 | 0.05 ± 0.01 | 0.17 ± 0.03 |
PANC-1 cells were treated for 24 h with 12.5 µM Lip-C6, 24 µM Lip-PDMP, 40 µM gemcitabine (Gem), or various combinations. Cells were harvested and lipids were extracted and analyzed using LC-MS/MS/MS. Abundance of different natural ceramide species relative to total cellular protein was determined (pmol/mg). One-way ANOVA:
p < 0.05 compared with control and Lip-Ghost,
p < 0.05 compared with Lip-Ghost only,
p < 0.05 compared with Lip-C6 (Lip-C6-containing combinations only),
p < 0.05 comparing triple combination with Lip-C6 + Lip-PDMP only,
p < 0.05 comparing triple combination with Lip-C6 + Gem and Lip-C6 + Lip-PDMP, n = 4.