Table 1. Amino-acid profiles of mixed neuronal cultures after treatment with xCT-inhibitors sorafenib and erastin.
| Amino acid | Control | Sorafenib 10 μM | Sorafenib 5 μM | Erastin 10 μM |
|---|---|---|---|---|
| n=12 | n=8 | n=10 | n=12 | |
| Glutamate | 100.00±27.40~ | 183.49±14.05, P=0.03218^ | 290.48±58.01, P=0.00518^ | 390.86±43.45, P=0.00002^ |
| α-Aminobutyric acid | 100.00±8.19~ | 147.11±13.03, P=0.00593^ | 30.04±7.08, P<0.00001 | 103.69±3.75, P=0.68846~ |
| Proline | 100.00±5.19~ | 130.82±8.73, P=0.00590^ | 159.98±7.96, P<0.00001^ | 103.59±3.78, P=0.58784~ |
| Serine | 100.00±6.09~ | 129.33±4.79, P=0.00306^ | 142.10±4.03, P=0.00002^ | 98.35±4.46, P=0.83189~ |
| Glutamine | 100.00±9.20~ | 125.72±6.85, P=0.05996^ | 234.19±5.44, P<0.00001^ | 93.63±8.15, P=0.61632~ |
| Taurine | 100.00±1.78~ | 122.65±3.39, P=0.00001^ | 117.07±3.45, P=0.00016~ | 105.78±2.85, P=0.10965~ |
| Phenylalanine | 100.00±1.59~ | 109.13±2.25, P=0.00392~ | 105.10±2.72, P=0.10772~ | 102.58±2.07, P=0.34757~ |
| Aspartate | 100.00±9.08~ | 108.21±7.46, P=0.53348~ | 119.68±9.76, P=0.15611~ | 114.01±6.37, P=0.22609~ |
| Arginine | 100.00±3.54~ | 106.80±2.15, P=0.16980~ | 65.34±1.76, P<0.00001 | 101.91±4.08, P=0.73408~ |
| Tyrosine | 100.00±1.65~ | 106.33±1.95, P=0.02756~ | 101.25±2.34, P=0.65815~ | 101.57±2.02, P=0.56312~ |
| Methionine | 100.00±1.91~ | 106.28±2.18, p=0.05184~ | 95.15±2.32, P=0.11844~ | 102.35±2.83, P=0.51026~ |
| Threonine | 100.00±1.57~ | 105.80±1.95, P=0.03645~ | 103.34±2.57, P=0.26301~ | 102.72±2.04, P=0.31588~ |
| Lysine | 100.00±1.74~ | 102.66±1.98, P=0.34607~ | 98.53±2.34, P=0.61395~ | 103.83±2.17, P=0.19347~ |
| Asparagine | 100.00±5.47~ | 101.53±3.49, P=0.83874~ | 79.08±2.62, P=0.00416 | 96.87±4.95, P=0.68151~ |
| Valine | 100.00±2.90~ | 98.67±2.88, P=0.76430~ | 66.59±1.42, P<0.00001 | 105.53±2.75, P=0.18892~ |
| Histidine | 100.00±1.77~ | 98.23±4.34, P=0.68729~ | 97.55±2.24, P=0.39382~ | 101.44±2.15, P=0.61966~ |
| Tryptophan | 100.00±2.57~ | 94.24±2.03, P=0.12967~ | 83.57±3.30, p=0.00073~ | 98.34±2.34, P=0.64500~ |
| Citrulline | 100.00±3.63~ | 94.24±4.05, P=0.32358~ | 99.64±2.45, P=0.93849~ | 100.26±2.99, P=0.95762~ |
| Leucine | 100.00±2.76~ | 90.58±2.53, P=0.03185~ | 50.33±1.43, P<0.00001 | 102.62±3.19, P=0.55057~ |
| Ornithine | 100.00±1.76~ | 85.73±2.48, P=0.00018~ | 80.98±1.72, P<0.00001~ | 101.70±2.32, P=0.57471~ |
| Isoleucine | 100.00±3.39~ | 83.65±2.82, P=0.00335~ | 42.37±1.35, P<0.00001 | 103.74±3.72, P=0.47555~ |
| 3-Methylhistidine | 100.00±2.10~ | 82.76±2.71, P=0.00010~ | 76.14±6.14, P=0.00078 | 96.58±2.55, P=0.32288~ |
| Alanine | 100.00±3.78~ | 77.66±3.79, P=0.00100 | 47.56±2.32, P<0.00001 | 102.62±2.07, P=0.55292~ |
| Glycine | 100.00±6.09~ | 61.26±6.24, P=0.00055 | 7.76±0.61, P<0.00001 | 99.95±5.61, P=0.99552~ |
| Cystathionine | 100.00±67.67~ | 60.32±56.42, P=0.68645 | 1382.22±86.94, P<0.00001^ | 0.00±0.00, P=0.15367 |
| Cystine | 100.00±9.07~ | 52.73±4.79, P=0.00092 | 18.61±0.79, P<0.00001 | 93.20±10.72, P=0.64189~ |
| Phosphoethanolamine | 100.00±43.56~ | 31.76±29.71, P=0.26730 | 61.69±41.13, P=0.53549 | 134.64±49.00, P=0.61143^ |
| Sarcosine | 100.00±94.84~ | 0.00±0.00, P=0.40485 | 0.00±0.00, P=0.34924 | 0.08±0.08, P=0.30354 |
| 1-Methylhistidine | 100.00±6.14~ | 0.00±0.00, P<0.00001 | 0.00±0.00, P<0.00001 | 99.10±5.38, P=0.91462~ |
| Anserine | 100.00±85.61~ | 0.00±0.00, P=0.35714 | 0.00±0.00, P=0.30092 | 0.00±0.00, P=0.25525 |
The levels of amino acids and metabolites in extracellular fluid are changed after treatment with different concentrations of sorafenib and erastin. Presented values are given as percent of untreated controls. The values are shown as mean ± standard error of the mean (SEM) and with P-values for two-sided t-tests. Upregulated amino acids are marked with ^; medium regulated amino acids (80–120% of controls) are marked with ~; downregulated amino acids are unmarked; alterations that are statistically significant are highlighted in bold font.