Table 3.
NMR bins and library matched metabolites that differentiate Luminal A and TNBC cell line responses to paclitaxel.
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|---|---|---|---|---|---|---|---|---|---|---|
| BT474 | MCF-7 | MDA-MB-231 | MDA-MB-468 | |||||||
|
| ||||||||||
| bin region | library matched metabolites | VIP | FC | VIP | FC | VIP | FC | VIP | FC | cell line response to paclitaxel |
| [7.64 .. 7.68] | 1-Methylhistidine | 1.1 | 1.6 | Increased in 468 | ||||||
| [1.87 .. 1.92] | Acetate, Lysine | 1.5 | −1.1 | Reduced in 231 | ||||||
| [1.45 .. 1.50] | Alanine | 2.2 | −1.1 | 3.3 | −1.1 | Reduced in 474 & 468 | ||||
| [3.78 .. 3.83] | Alanine, Cystathionine, Glucose, Glutathione, UDP-glucose, UDP-N-Acetylglucosamine | 2.4 | 1.1 | Increased in 474 | ||||||
| [3.72 .. 3.78] | Alanine, Glutamine, Glutathione, Glucose, Leucine, Glutamate | 4.5 | 1.1 | 2.5 | 1.0 | Increased in 231 & 468 | ||||
| [1.34 .. 1.38] | Alloisoleucine, Acetoin | 1.4 | 1.0 | 1.4 | −1.1 | Increased in 474; Reduced in 231 | ||||
| [2.62 .. 2.68] | Aspartate, Citrate, Unknown | 1.0 | 1.0 | Increased in MCF | ||||||
| [3.17 .. 3.23] | Choline, O-Acetylcholine, O-Phosphocholine, sn-Glycerophosphocholine | 3.7 | 1.1 | 1.8 | −1.0 | 2.7 | 1.1 | Increased in 474 & 468; Reduced in 231 | ||
| [3.90 .. 3.95] | Creatine, Glucose, Glycolate, UDP-N-Acetylglucosamine, Uridine, Tyrosine | 1.2 | −1.0 | Reduced in MCF | ||||||
| [3.10 .. 3.15] | Cystathionine, Histidine, Cystine, Phenylalanine, Ethylmalonate | 1.2 | −1.1 | Reduced in 231 | ||||||
| [3.70 .. 3.72] | Glucose | 2.1 | 1.3 | 1.3 | −1.0 | Increased in 474; Reduced in 468 | ||||
| [5.18 .. 5.24] | Glucose | 1.3 | 1.3 | Increased in 474 | ||||||
| [3.39 .. 3.44] | Glucose, Proline | 2.3 | 1.2 | 1.3 | 1.0 | Increased in 474 & 468 | ||||
| [3.44 .. 3.48] | Glucose, UDP-Glucose | 1.8 | −1.0 | Reduced in 468 | ||||||
| [3.83 .. 3.85] | Glucose, UDP-Glucose | 1.1 | 1.1 | Increased in 468 | ||||||
| [3.85 .. 3.90] | Glucose, UDP-Glucose | 3.2 | 1.2 | 2.3 | 1.1 | 1.5 | 1.0 | Increased in 474, 231 & 468 | ||
| [2.08 .. 2.11] | Glutamate | 1.4 | 1.1 | Increased in 468 | ||||||
| [2.30 .. 2.32] | Glutamate | 1.2 | −1.1 | Reduced in 231 | ||||||
| [2.32 .. 2.37] | Glutamate | 1.7 | −1.0 | 2.3 | 1.0 | 2.2 | −1.0 | 2.4 | 1.1 | Reduced in 474 & 231; Increased in MCF & 468 |
| [2.11 .. 2.17] | Glutamate, Glutamine | 2.4 | 1.1 | 2.2 | −1.0 | Increased in 474; Reduced in MCF | ||||
| [2.47 .. 2.49] | Glutamine | 1.0 | 1.0 | Increased in 231 | ||||||
| [2.42 .. 2.47] | Glutamine, Glutamate | 2.4 | 1.1 | 3.9 | 1.1 | Increased in 474 & 231 | ||||
| [3.50 .. 3.55] | Glycine, myo-Inositol, Glucose | 3.0 | −1.0 | Reduced in 468 | ||||||
| [1.18 .. 1.23] | Isoleucine, Overlap | 1.9 | −1.1 | Reduced in MCF & 468 | ||||||
| [1.23 .. 1.27] | Isoleucine | 1.5 | 1.1 | 1.7 | −1.1 | Increased in 474; Reduced in 468 | ||||
| [1.27 .. 1.29] | Isoleucine | 1.6 | −1.2 | Reduced in 468 | ||||||
| [1.40 .. 1.45] | Isoleucine, Alloisoleucine | 1.8 | 1.1 | 1.4 | −1.0 | Increased in 474; Reduced in 468 | ||||
| [0.91 .. 0.97] | Isoleucine, Leucine | 2.6 | −1.1 | 1.3 | 1.0 | 1.7 | −1.0 | Reduced in MCF & 468; Increased in 231 | ||
| [3.65 .. 3.70] | Isoleucine, sn-Glycero-3-phosphocholine, Unknown | 2.6 | 1.2 | Increased in 474 | ||||||
| [4.07 .. 4.13] | Lactate | 2.7 | −1.1 | 1.7 | 1.2 | 2.1 | −1.0 | Reduced in MCF & 468; Increased in 231 | ||
| [1.29 .. 1.34] | Lactate, Threonine | 5.7 | −1.1 | 5.3 | −1.1 | Reduced in MCF & 468 | ||||
| [0.70 .. 0.72] | Lipoproteins | 1.0 | −1.1 | Reduced in 468 | ||||||
| [0.72 .. 0.74] | Lipoproteins | 1.0 | −1.1 | Reduced in 468 | ||||||
| [0.74 .. 0.76] | Lipoproteins | 1.1 | −1.1 | Reduced in 468 | ||||||
| [0.76 .. 0.78] | Lipoproteins | 1.0 | −1.1 | Reduced in 468 | ||||||
| [0.78 .. 0.80] | Lipoproteins | 1.1 | −1.1 | Reduced in 468 | ||||||
| [0.89 .. 0.91] | Lipoproteins | 1.3 | −1.0 | Reduced in 468 | ||||||
| [1.70 .. 1.76] | Lysine | 1.1 | −1.0 | 1.0 | −1.0 | Reduced in MCF & 468 | ||||
| [1.92 .. 1.95] | Lysine | 1.2 | −1.1 | Reduced in 231 | ||||||
| [3.60 .. 3.65] | myo-Inositol | 4.0 | 1.1 | 1.8 | −1.0 | Increased in MCF; Reduced in 468 | ||||
| [3.23 .. 3.29] | myo-Inositol, Betaine, Taurine, Trimethylamine-N-oxide (TMAO) | 1.3 | −1.0 | Reduced in 468 | ||||||
| [4.02 .. 4.07] | myo-Inositol, Creatinine | 1.9 | −1.1 | Reduced in 468 | ||||||
| [3.55 .. 3.60] | myo-Inositol, Threonine, O-Phosphocholine, sn-Glycero-3-phosphocholine, Valine | 2.1 | 1.1 | Increased in 474 | ||||||
| [1.55 .. 1.60] | Overlap | 1.0 | −1.1 | Reduced in 231 | ||||||
| [4.94 .. 5.00] | Overlap | 0.7 | 2.2 | Increased in 474 | ||||||
| [5.63 .. 5.69] | Overlap | 0.3 | −2.2 | 0.7 | −2.2 | Reduced in 474 & 231 | ||||
| [5.69 .. 5.72] | Overlap | 0.2 | −2.1 | 0.4 | −2.0 | Reduced in 474 & 231 | ||||
| [5.72 .. 5.74] | Overlap | 0.3 | −2.2 | Reduced in 231 | ||||||
| [1.95 .. 1.97] | Proline | 1.1 | −1.1 | 1.0 | −1.0 | Reduced in 231 & 468 | ||||
| [1.97 .. 1.99] | Proline | 1.3 | −1.1 | 1.1 | −1.0 | 1.0 | −1.0 | Reduced in MCF, 231 & 468 | ||
| [1.99 .. 2.03] | Proline, N-Acetylamino acids, Glutamate | 2.9 | −1.1 | Reduced in MCF | ||||||
| [2.37 .. 2.42] | Pyroglutamate | 2.2 | 1.1 | Increased in 474 | ||||||
| [4.30 .. 4.34] | sn-Glycero-3-phosphocholine | 1.0 | 1.1 | Increased in 231 | ||||||
| [6.86 .. 6.92] | Tyrosine | 1.0 | −1.1 | Reduced in MCF | ||||||
| [4.13 .. 4.18] | UDP-Glucuronate, Pyroglutamate, O-phosphocholine, Proline | 1.7 | −1.0 | 1.3 | 1.0 | 1.0 | 1.1 | 1.3 | 1.0 | Reduced in 474; Increased in MCF, 231 & 468 |
| [5.48 .. 5.52] | UDP-N-Acetylglucosamine | 1.1 | −1.2 | Reduced in 231 | ||||||
| [4.26 .. 4.30] | UDP-N-Acetylglucosamine, UDP-Glucose, UDP-Glucuronate, UDP-Galactose, ATP | 1.0 | −1.1 | Reduced in 474 | ||||||
| [5.79 .. 5.85] | Unknown | 1.0 | −1.9 | Reduced in 231 | ||||||
| [9.21 .. 9.24] | Unknown | 0.5 | 4.1 | Increased in 468 | ||||||
| [1.02 .. 1.07] | Valine | 1.4 | −1.1 | 1.5 | −1.0 | Reduced in MCF & 468 | ||||
| [2.26 .. 2.30] | Valine | 1.1 | 1.1 | 1.2 | −1.0 | Increased in 474; Reduced in 231 | ||||
| [0.97 .. 1.02] | Valine, Isoleucine | 2.0 | −1.1 | 1.5 | −1.0 | Reduced in 468 | ||||
The metabolites listed were determined to be important in differentiating within a specific cell line between paclitaxel treated cells and the non-treated control at 48 hrs - based on VIP ≥ 1 with a confidence interval not including 0 (p-values were not calculated due to the small sample sizes).
*
A positive fold change indicates that the median bin intensity in cells treated with paclitaxel > median of signals in cells incubated in media only for each line. VIP = variable influence on projection. FC = fold change. Cell line names are abbreviated as 474 (BT474), MCF (MCF-7), 231 (MDA-MB-231) and 468 (MDA-MB-468) in the last column listing cell line responses with paclitaxel treatment. NMR bins identified as “Overlap” could not be assigned to metabolites distinctively using the NMR library and further 2D experiments are needed for confirmed identification.