Table 1.
Intracellular metabolites significantly correlated with doxorubicin treatment across drug-sensitive and drug-resistant cell lines.
| Metabolite (Name_Ontology Level_Retention Time_Mass) | MDA-MB-231 | DOX-RES-50 | DOX-RES-100 | |||
|---|---|---|---|---|---|---|
| Correlation | p-Value | Correlation | p-Value | Correlation | p-Value | |
| Methylthioadenosine_OL1_4.92_297.0893 n | −0.81 | 0.00001554 | −0.72 | 0.0003888 | −0.68 | 0.0010676 |
| N-Acetylmethionine_OL1_4.71_191.0610 n | −0.77 | 0.00007602 | −0.50 | 0.023791 | −0.33 | 0.15296 |
| Anthranilate_OL1_5.84_137.0474 n | −0.76 | 0.00009184 | 0.15 | 0.53421 | −0.27 | 0.24814 |
| 12-Hydroxydodecanoic Acid_OL2b_5.12_261.1439 m/z | −0.76 | 0.00011148 | −0.30 | 0.19307 | 0.29 | 0.21246 |
| 2-Octenedioic Acid_OL2b_1.44_137.0594 m/z | −0.74 | 0.00019629 | −0.31 | 0.17985 | −0.37 | 0.11085 |
| Indoleacrylic Acid_OL2b_4.34_187.0632 n | −0.74 | 0.00020622 | −0.35 | 0.13308 | −0.50 | 0.023743 |
| 2-Aminocaprylic Acid_OL1_6.37_160.1329 m/z | −0.72 | 0.00037329 | −0.39 | 0.088065 | −0.49 | 0.029253 |
| Adenosine 2′,3′-Cyclic Phosphate_OL2b_2.91_330.0592 m/z | 0.71 | 0.00047735 | 0.21 | 0.37223 | 0.83 | 0.00000680 |
| Trans-3-Hydroxycinnamate_OL2b_1.56_164.0473 n | −0.70 | 0.00053789 | −0.42 | 0.062772 | −0.44 | 0.051265 |
| Pyridoxine_OL1_1.27_169.0735 n | −0.70 | 0.00054082 | 0.09 | 0.70269 | 0.06 | 0.79124 |
| Spermidine_OL2b_3.42_146.1649 m/z | −0.68 | 0.00099902 | −0.14 | 0.54993 | 0.16 | 0.5026 |
| Cytidine_OL1_0.69_243.0848 n | 0.67 | 0.0013015 | 0.18 | 0.44717 | 0.16 | 0.50397 |
| Threonine_OL2a_0.67_158.0211 m/z | −0.66 | 0.0015141 | −0.47 | 0.037284 | −0.37 | 0.10919 |
| 2-Octenedioic Acid_OL2b_3.72_172.0730 n | −0.66 | 0.0016946 | −0.34 | 0.13976 | 0.30 | 0.19228 |
| 5-Hydroxyindoleacetate_OL2b_2.91_191.0575 n | −0.66 | 0.001717 | −0.28 | 0.23609 | −0.20 | 0.38949 |
| Indoleacetaldehyde_OL1_4.34_160.0754 m/z | −0.65 | 0.0017981 | −0.15 | 0.5315 | −0.26 | 0.27521 |
| N-Acetylaspartate_OL2a_0.83_198.0368 m/z | 0.65 | 0.0018161 | 0.27 | 0.2445 | 0.43 | 0.059134 |
| Leucine_OL1_1.70_131.0944 n | −0.65 | 0.0019876 | −0.38 | 0.097942 | −0.41 | 0.071259 |
| Hydroxyphenyllactate_OL1_4.59_205.0468 m/z | −0.65 | 0.0020371 | −0.23 | 0.33412 | −0.44 | 0.05153 |
| Indoleacetaldehyde_OL2b_2.46_159.0682 n | −0.63 | 0.0030782 | 0.06 | 0.78868 | 0.06 | 0.78725 |
| Octanoyl-L-Carnitine_OL1_9.20_288.2162 m/z | −0.63 | 0.0031425 | −0.42 | 0.067438 | −0.25 | 0.29713 |
| Isoleucyl-Leucine_OL2b_5.43_245.1852 m/z | −0.62 | 0.0035538 | −0.66 | 0.0016847 | −0.08 | 0.73277 |
| L-Tryptophan_OL1_4.34_204.0897 n | −0.62 | 0.0036778 | −0.24 | 0.30013 | −0.38 | 0.1017 |
| L-Phenylalanine_OL1_3.22_165.0787 n | −0.61 | 0.0042322 | −0.48 | 0.033566 | −0.54 | 0.014204 |
| Deoxyadenosine_OL2b_3.57_252.1084 m/z | −0.60 | 0.0048732 | −0.20 | 0.39106 | −0.29 | 0.22223 |
| L-Methionine_OL2a_1.07_172.0400 m/z | −0.59 | 0.0057758 | −0.37 | 0.11265 | −0.25 | 0.28305 |
| Pantothenate_OL1_4.04_219.1102 n | −0.58 | 0.0068454 | 0.12 | 0.60768 | 0.24 | 0.31459 |
| Trans-Cinnamic Acid_OL2b_3.24_148.0522 n | −0.58 | 0.0069352 | −0.35 | 0.12974 | −0.42 | 0.063941 |
| Pyridoxal_OL2b_2.81_150.0548 m/z | −0.58 | 0.0079745 | 0.22 | 0.36202 | 0.07 | 0.77067 |
| Leucyl-Leucine_OL1_5.89_245.1852 m/z | −0.57 | 0.0083982 | −0.34 | 0.14013 | −0.28 | 0.23375 |
| Indole-3-Aldehyde_OL2b_4.34_146.0599 m/z | −0.56 | 0.0094943 | −0.24 | 0.31034 | −0.33 | 0.15284 |
| 2-Octenedioic Acid_OL2a_6.83_195.0622 m/z | 0.56 | 0.010025 | −0.17 | 0.47878 | −0.38 | 0.093781 |
| N-Acetylaspartate_OL1_1.11_175.0478 n | 0.54 | 0.013375 | 0.61 | 0.0046458 | 0.50 | 0.025329 |
| Spermidine_OL2a_0.65_145.1575 n | −0.54 | 0.013553 | −0.14 | 0.56286 | 0.05 | 0.82905 |
| Phenylacetylglycine_OL1_5.92_193.0737 n | −0.54 | 0.014787 | 0.16 | 0.48874 | 0.15 | 0.5273 |
| Dodecenoylcarnitine_OL1_11.80_342.2630 m/z | −0.53 | 0.015577 | −0.39 | 0.087782 | −0.09 | 0.70138 |
| Indole-3-Ethanol_OL2b_4.34_144.0806 m/z | −0.52 | 0.017664 | −0.22 | 0.34956 | −0.26 | 0.26126 |
| Guanine_OL2b_3.62_152.0563 m/z | −0.51 | 0.020217 | −0.21 | 0.36735 | −0.18 | 0.45806 |
| L-Tyrosine_OL2b_3.37_182.0807 m/z | −0.51 | 0.020866 | −0.09 | 0.70388 | −0.20 | 0.40599 |
| Threonine_OL1_1.07_102.0548 m/z | −0.51 | 0.021699 | 0.14 | 0.56117 | −0.14 | 0.56762 |
| Butenylcarnitine_OL2a_2.71_262.1642 m/z | −0.51 | 0.022923 | 0.17 | 0.47043 | 0.35 | 0.126 |
| Creatine_OL2a_0.51_263.1455 m/z | −0.50 | 0.024141 | 0.39 | 0.093473 | 0.85 | 0.00000202 |
| 5-Oxoproline_OL2b_0.77_129.0424 n | −0.49 | 0.026792 | −0.10 | 0.68462 | −0.04 | 0.85349 |
| S-Adenosylhomocysteine_OL1_2.09_384.1212 n | −0.48 | 0.030318 | 0.21 | 0.38359 | −0.07 | 0.75567 |
| Propionyl-L-Carnitine_OL1_2.09_218.1387 m/z | −0.48 | 0.033559 | 0.34 | 0.1442 | 0.15 | 0.52079 |
| Trigonelline_OL2b_5.41_138.0546 m/z | 0.47 | 0.035034 | −0.35 | 0.12744 | −0.02 | 0.93339 |
| Creatine_OL2a_0.49_132.0766 m/z | −0.47 | 0.036563 | 0.43 | 0.055497 | 0.82 | 0.00000987 |
| L-Phenylalanine_OL2a_3.22_331.1643 m/z | −0.47 | 0.0368 | −0.38 | 0.10306 | −0.51 | 0.022902 |
| N-Acetylhistidine_OL2b_2.24_198.0872 m/z | −0.46 | 0.039432 | 0.28 | 0.23266 | −0.02 | 0.92921 |
| Spermidine_OL2a_0.49_73.5862 m/z | −0.46 | 0.040849 | 0.10 | 0.66657 | 0.22 | 0.35548 |
| Pantetheine_OL2b_9.30_261.1260 m/z | 0.46 | 0.041443 | −0.08 | 0.74182 | 0.18 | 0.43803 |
| Acetyl-Dl-Carnitine_OL1_1.01_204.1229 m/z | −0.46 | 0.041794 | −0.16 | 0.49485 | 0.13 | 0.57551 |
| 1-Aminocyclopropanecarboxylic Acid_OL2a_0.77_84.0443 m/z | −0.46 | 0.043552 | −0.02 | 0.93018 | 0.00 | 0.99278 |
| Hexanoylcarnitine_OL1_6.23_260.1850 m/z | −0.45 | 0.047391 | −0.24 | 0.2993 | 0.19 | 0.4278 |
| 4-Acetamidobutanoic Acid_OL2b_3.37_146.0809 m/z | −0.41 | 0.075098 | 0.51 | 0.020527 | 0.38 | 0.099942 |
| Hexanoylcarnitine_OL1_6.53_260.1850 m/z | −0.40 | 0.079541 | −0.33 | 0.15004 | −0.55 | 0.011742 |
| Maleic Acid_OL2a_1.11_134.0445 m/z | 0.39 | 0.087469 | 0.52 | 0.017879 | 0.41 | 0.074901 |
| Glutamyl-Valine_OL2b_3.72_247.1284 m/z | −0.39 | 0.090678 | 0.39 | 0.090925 | 0.53 | 0.016339 |
| 2-Hydroxytetradecanoic Acid_OL2a_14.99_227.1998 m/z | 0.38 | 0.099925 | −0.06 | 0.81747 | 0.51 | 0.021926 |
| Acetyl-DL-Carnitine_OL1_0.71_203.1156 n | −0.36 | 0.11621 | 0.46 | 0.039795 | 0.00 | 0.99876 |
| Butanoylcarnitine_OL1_3.64_231.1467 n | −0.34 | 0.14514 | 0.41 | 0.072478 | 0.48 | 0.032961 |
| Glycoursodeoxycholic Acid_OL2b_14.05_449.3136 n | −0.32 | 0.16414 | 0.47 | 0.037037 | −0.09 | 0.71422 |
| Sorbitol_OL1_0.65_182.0786 n | 0.30 | 0.19459 | −0.07 | 0.78117 | 0.47 | 0.037825 |
| Betaine_OL2a_0.67_140.0680 m/z | −0.30 | 0.20182 | −0.56 | 0.01107 | −0.03 | 0.90492 |
| Cadaverine_OL2a_0.83_102.1150 m/z | −0.30 | 0.20579 | 0.16 | 0.49012 | 0.55 | 0.011389 |
| 2-Methylbutyroylcarnitine_OL1_4.84_246.1696 m/z | −0.28 | 0.23419 | 0.55 | 0.012568 | 0.38 | 0.095206 |
| Tetradecenoyl-L-Carnitine_OL1_12.82_370.2941 m/z | −0.27 | 0.24147 | −0.61 | 0.0043994 | 0.00 | 0.99629 |
| Creatinine_OL1_0.67_136.0479 m/z | 0.27 | 0.24167 | 0.20 | 0.38662 | 0.45 | 0.046976 |
| Citric Acid_OL2a_0.98_176.0083 m/z | −0.27 | 0.25513 | 0.27 | 0.24076 | −0.45 | 0.048451 |
| Spermine_OL2b_1.97_202.2156 n | −0.25 | 0.27928 | 0.17 | 0.48187 | 0.49 | 0.028223 |
| 7-Ketodeoxycholic Acid_OL2b_15.51_406.2712n | 0.25 | 0.28049 | −0.22 | 0.34463 | −0.47 | 0.038013 |
| Indolelactic Acid_OL1_7.14_205.0735 n | −0.25 | 0.28598 | −0.26 | 0.26977 | −0.68 | 0.00088093 |
| 2-Hydroxytetradecanoic Acid_OL2a_15.04_283.1663 m/z | 0.25 | 0.29295 | −0.12 | 0.60035 | 0.55 | 0.012847 |
| Glutarate_OL1_2.66_115.0388 m/z | −0.24 | 0.30605 | 0.52 | 0.018071 | 0.55 | 0.011919 |
| Cytosine_OL1_1.04_112.0503 m/z | 0.22 | 0.34136 | 0.83 | 0.00000607 | 0.61 | 0.0043897 |
| B-Nicotinamide Adenine Dinucleotide_OL2a_3.06_333.5691 m/z | −0.18 | 0.44516 | 0.06 | 0.81435 | 0.51 | 0.02153 |
| Cadaverine_OL2a_0.40_102.1150 m/z | −0.18 | 0.4511 | 0.21 | 0.36841 | 0.59 | 0.0061138 |
| Xanthine_OL1_1.54_153.0403 m/z | −0.15 | 0.52016 | 0.69 | 0.0007609 | 0.28 | 0.23164 |
| Creatine_OL1_0.69_131.0693 n | 0.04 | 0.8519 | 0.25 | 0.27987 | 0.46 | 0.039218 |
| Docosatrienoic Acid_OL2a_16.73_299.2728 m/z | 0.00 | 0.99386 | −0.58 | 0.0073867 | 0.26 | 0.27377 |
Metabolites are named in the following format: metabolite_ontology level_retention time_mass. An “m/z” following the mass denotes an ion mass, whereas an “n” denotes a neutral mass. The names given for each match are based on the names of the reference standards run on our UHPLC-HRMS platform or the names provided in public databases. This method does not necessarily differentiate between some isomeric forms, such as D and L enantiomers. Positive correlation values indicate metabolites that positively correlate with doxorubicin treatment.