5-ALA Is a Potent Lactate Dehydrogenase Inhibitor but Not a Substrate: Implications for Cell Glycolysis and New Avenues in 5-ALA-Mediated Anticancer Action
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Chemicals and Reagents
2.2. Cell Culture
2.3. Metabolic Assays
2.4. Spectrophotometric Assesment of LDH Kinetics with or without Inhibitors, in Purified Enzyme Assays or Cell Lysates
2.5. Cytotoxicity by 5-ALA Induced Glycolysis Inhibition
2.6. PDT Experiments
2.7. Flow Cytometry
2.8. Computational Methods
2.9. NMR Experiments
3. Results
Molecular Modeling of 5-ALA in Complex with LDH-A
4. Discussion
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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Enzyme | Cell Lysates | ||||
---|---|---|---|---|---|
U87 | T98G | Ln18 | M059K | ||
No inhib. | −2.28 | −1.43 | −1.20 | −1.48 | −1.47 |
+5-ALA | −0.51 | −0.32 | −0.57 | −0.47 | −0.53 |
+OXM | −0.44 | −0.73 | −0.25 | −0.24 | −0.32 |
+TART | −0.32 | −0.24 | −0.26 | −0.17 | −0.29 |
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Grigalavicius, M.; Ezzatpanah, S.; Papakyriakou, A.; Raabe, T.T.H.; Yannakopoulou, K.; Theodossiou, T.A. 5-ALA Is a Potent Lactate Dehydrogenase Inhibitor but Not a Substrate: Implications for Cell Glycolysis and New Avenues in 5-ALA-Mediated Anticancer Action. Cancers 2022, 14, 4003. https://doi.org/10.3390/cancers14164003
Grigalavicius M, Ezzatpanah S, Papakyriakou A, Raabe TTH, Yannakopoulou K, Theodossiou TA. 5-ALA Is a Potent Lactate Dehydrogenase Inhibitor but Not a Substrate: Implications for Cell Glycolysis and New Avenues in 5-ALA-Mediated Anticancer Action. Cancers. 2022; 14(16):4003. https://doi.org/10.3390/cancers14164003
Chicago/Turabian StyleGrigalavicius, Mantas, Somayeh Ezzatpanah, Athanasios Papakyriakou, Tine Therese Henriksen Raabe, Konstantina Yannakopoulou, and Theodossis A. Theodossiou. 2022. "5-ALA Is a Potent Lactate Dehydrogenase Inhibitor but Not a Substrate: Implications for Cell Glycolysis and New Avenues in 5-ALA-Mediated Anticancer Action" Cancers 14, no. 16: 4003. https://doi.org/10.3390/cancers14164003