Cell Metabolomics Reveals the Potential Mechanism of Aloe Emodin and Emodin Inhibiting Breast Cancer Metastasis
Abstract
:1. Introduction
2. Results
2.1. Metabolomic Comparison of Single-Culture and Co-Culture MCF-7 Cells
2.2. Cytotoxicity of AE and EMD
2.3. AE and EMD Reduce the Adhesion of MCF-7 Cells to HUVEC Cells
2.4. AE and EMD Inhibit the Invasion and Metastasis of MCF-7 Cells
2.5. Effects of AE and EMD on Metabolism of MCF-7 Cells
2.6. Quantitative Analysis of Biomarkers
3. Discussion
4. Materials and Methods
4.1. Materials
4.2. Cell Culture
4.3. Cytotoxicity Assay
4.4. Adhesion Assay
4.5. Invasion Assay
4.6. Activity Determination of MMP-2, MMP-9, and VEGF
4.7. Soft Agar Colony Formation
4.8. Cell Sample Preparation for Metabolomic Analyses
4.9. UPLC-MS Conditions
4.10. Data Processing and Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Mode | Metabolites | RT (min) | Measured Mass (Da) | Mass Error (ppm) | AE | EMD | DOX | Pathway |
---|---|---|---|---|---|---|---|---|
ESI+ | Spermine | 0.50 | 203.2238 | 1.0 | ↓ * | - | ↓ *** | Polyamine metabolism |
Arginine | 0.65 | 174.1128 | 6.3 | - | - | ↓ ** | Arginine biosynthesis | |
Creatine | 0.45 | 132.1000 | −8.3 | ↓ * | - | ↓ ** | Glycine, serine, and threonine metabolism | |
Methionine | 1.12 | 150.0589 | 0.0 | ↓ * | - | ↓ ** | Methionine cycle | |
Glutathione | 1.39 | 308.0916 | 0.0 | ↓ ** | ↓ * | ↓ ** | Glutathione metabolism | |
Isoleucine | 1.93 | 132.1031 | 4.5 | ↑ *** | - | ↑ *** | Valine, leucine, and isoleucine degradation | |
2-phenylglycine | 2.16 | 152.0700 | 4.8 | - | - | ↑ ** | - | |
Pyridoxine | 2.16 | 170.0825 | 4.7 | ↑ * | - | ↑ *** | Vitamin B6 metabolism | |
Adenine | 1.26 | 136.0630 | 5.1 | ↓ ** | - | ↓ *** | Purine metabolism | |
ADP | 4.47 | 428.0375 | 0.7 | ↓ * | - | ↓ * | Purine metabolism | |
Oxidized glutathione | 4.47 | 613.1589 | −1.5 | ↑ * | ↑ * | ↑ * | Glutathione metabolism | |
Phenylalanine | 4.70 | 166.0876 | 4.8 | ↑ *** | ↑ * | ↑ *** | Phenylalanine metabolism | |
Guanine | 4.70 | 152.0580 | 5.3 | - | ↑ ** | - | Purine metabolism | |
1H-indole-3-carboxaldehyde | 5.29 | 146.0614 | 5.5 | ↑ * | - | ↑ *** | Tryptophan metabolism | |
Indoleacrylic acid | 5.29 | 188.0723 | 5.8 | ↑ ** | - | ↑ *** | Tryptophan metabolism | |
Phytosphingosine | 9.54 | 318.3009 | 0.3 | ↑ *** | ↑ * | ↑ *** | Sphingolipid metabolism | |
ESI− | Glutamic acid | 0.73 | 146.0455 | 1.4 | - | - | ↓ *** | D-glutamine and D-glutamate metabolism |
Tyrosine | 2.49 | 180.0662 | 0.6 | ↑ *** | - | ↑ *** | Tyrosine metabolism | |
Xanthine | 2.49 | 151.0257 | 0.7 | ↓ *** | - | ↓ *** | Purine metabolism | |
Glutathione | 1.39 | 306.0759 | −0.3 | ↓ * | ↓ * | ↓ *** | Glutathione metabolism | |
Oxidized glutathione | 4.47 | 611.1439 | −0.3 | ↑ * | - | ↓ * | Glutathione metabolism | |
Malic acid | 0.88 | 133.0130 | −5.3 | ↓ *** | ↓ * | ↓ *** | Citrate cycle (TCA cycle) | |
Phenylalanine | 4.62 | 164.0720 | 4.8 | ↑ ** | ↑ * | ↑ *** | Phenylalanine metabolism | |
Hypoxanthine | 1.93 | 135.0308 | 0.7 | ↓ *** | ↓ * | ↓ *** | Purine metabolism | |
Tryptophan | 5.29 | 203.0820 | −0.5 | ↑ ** | - | ↑ *** | Tryptophan metabolism | |
Pantothenic acid | 4.96 | 218.1029 | 0.5 | ↑ *** | ↓ * | ↑ *** | Pantothenate and CoA biosynthesis | |
Azelaic acid | 7.12 | 187.0970 | 0.0 | ↑ * | - | ↑ * | - | |
S-adenosylhomo-cysteine | 4.47 | 383.1134 | −1.0 | ↓ * | ↓ * | ↓ *** | Methionine cycle | |
Cytosine | 0.88 | 110.0356 | 1.8 | ↓ * | - | ↓ *** | Pyrimidine metabolism | |
N-formyl-L-glutamic acid | 1.26 | 174.0402 | 0.0 | ↓ *** | ↑ *** | ↓ *** | Histidine metabolism | |
Folic acid | 5.47 | 440.1315 | −0.9 | ↑ ** | - | ↑ *** | Folate biosynthesis | |
Inosine | 4.62 | 267.0735 | 2.2 | ↑ * | - | ↑ ** | Purine metabolism | |
Citric acid | 1.72 | 191.0192 | 0.0 | ↑ * | - | ↑ * | Citrate cycle (TCA cycle) | |
Guanosine | 4.62 | 282.0839 | 0.4 | ↓ * | ↓ * | ↓ * | Purine metabolism |
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Cheng, G.; Liu, Z.; Zheng, Z.; Song, F.; Zhuang, X.; Liu, S. Cell Metabolomics Reveals the Potential Mechanism of Aloe Emodin and Emodin Inhibiting Breast Cancer Metastasis. Int. J. Mol. Sci. 2022, 23, 13738. https://doi.org/10.3390/ijms232213738
Cheng G, Liu Z, Zheng Z, Song F, Zhuang X, Liu S. Cell Metabolomics Reveals the Potential Mechanism of Aloe Emodin and Emodin Inhibiting Breast Cancer Metastasis. International Journal of Molecular Sciences. 2022; 23(22):13738. https://doi.org/10.3390/ijms232213738
Chicago/Turabian StyleCheng, Guorong, Zhiqiang Liu, Zhong Zheng, Fengrui Song, Xiaoyu Zhuang, and Shu Liu. 2022. "Cell Metabolomics Reveals the Potential Mechanism of Aloe Emodin and Emodin Inhibiting Breast Cancer Metastasis" International Journal of Molecular Sciences 23, no. 22: 13738. https://doi.org/10.3390/ijms232213738