The Interplay of Dysregulated pH and Electrolyte Imbalance in Cancer
Abstract
1. Introduction
2. Extracellular Acidity and pH Sensors
3. The Impact of pH on the Proliferation and the Survival of Cancer Cells
4. Tumor Metabolism
5. Effect of pH on Tumor Metabolism
Carbonic Anhydrase Enzyme
6. pH-Tumor Angiogenesis interactions
7. Electrolytes-pH Dynamics interactions
7.1. Sodium-Ion (Na+)
7.2. Potassium Ion (K+)
7.3. Calcium Ion (Ca2+)
7.4. Chloride Ion (Cl−)
8. Conclusions
Funding
Acknowledgments
Conflicts of Interest
References
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The Name of Proteins | Modulators |
---|---|
Anion exchanger family (bicarbonate transporter family) | Acetazolamide, niflumic acid [101] |
The Name of Proteins | Modulators |
---|---|
Voltage-gated sodium channels (NaV) | Tetrodotoxin (TTX) |
Sodium-calcium exchanger (Na+/Ca2+ exchangers; NCX) | Bepridil, 3′,4′-dichlorobenzamil hydrochloride, KB-R7943, SEA0400, SN-6, YM-244769 [147,148,149,150] |
Sodium–hydrogen antiporter or sodium–proton exchanger (Na+/H+ exchanger; NHE) | cariporide, amiloride; HMA (5-(N,N-hexametylene)-amiloride); Phx-3; Compound 9t [1,116,123,128,151,152] |
Na+/K+-ATPase (sodium - potassium adenosine triphosphatase; the Na+/K+ pump or sodium–potassium pump) | Digoxin; Ouabain; 3,4,5,6-tetrahydroxyxanthone [153,154,155] |
Potassium-dependent sodium-calcium exchanger | - |
The Name of Proteins | Modulators | |
---|---|---|
Voltage-gated potassium channel (VGKCs) | Astemizole | |
Calcium-activated potassium channel | BK channel (Maxi-K, slo1) | Charybdotoxin (blocker) [166] |
SK channels | Rottlerin (mallotoxin) (activator) [167] | |
IK channel | ||
Inwardly rectifying potassium channel | The renal outer medullary potassium channel (ROMK) | Nicorandil (could be used as adjuvant therapy to anticancer to prevent cardiotoxicity) [168,169] |
G protein-coupled inwardly rectifying potassium channels (GIRKs) | ||
ATP-sensitive potassium channel (KATP channel) | ||
Tandem pore domain potassium channel | Fluoxetine [170,171,172] |
The Name of Proteins | Modulators | |
---|---|---|
voltage-gated calcium channel | L-type calcium channel | Mibefradil [196] |
P-type calcium channel/Q-type calcium channel | ||
N-type calcium channel | ||
R-type calcium channel | ||
T-type calcium channel | ||
ligand-gated calcium channel | IP3 receptor (Inositol trisphosphate receptor (InsP3R)) | Carboxyamidotriazole and dihydropyridine |
Ryanodine receptor | ||
Two-pore channel | ||
cation channels of sperm; Catsper channels (CatSper) | ||
store-operated channels |
The Name of Proteins | Modulators |
---|---|
CLC family | 5-nitro-2-3-phenylpropylamino benzoic acid (NPPB), [219] |
Epithelial Chloride Channel (E-ClC) family | sodium butyrate [220] |
Chloride Intracellular Ion Channel (CLIC) Family | R (+) Indanyloxyacetic acid 94 (R(+)-IAA-94) |
Cystic fibrosis transmembrane conductance regulator (CFTR) | - |
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Share and Cite
Alfarouk, K.O.; Ahmed, S.B.M.; Ahmed, A.; Elliott, R.L.; Ibrahim, M.E.; Ali, H.S.; Wales, C.C.; Nourwali, I.; Aljarbou, A.N.; Bashir, A.H.H.; et al. The Interplay of Dysregulated pH and Electrolyte Imbalance in Cancer. Cancers 2020, 12, 898. https://doi.org/10.3390/cancers12040898
Alfarouk KO, Ahmed SBM, Ahmed A, Elliott RL, Ibrahim ME, Ali HS, Wales CC, Nourwali I, Aljarbou AN, Bashir AHH, et al. The Interplay of Dysregulated pH and Electrolyte Imbalance in Cancer. Cancers. 2020; 12(4):898. https://doi.org/10.3390/cancers12040898
Chicago/Turabian StyleAlfarouk, Khalid O., Samrein B. M. Ahmed, Ahmed Ahmed, Robert L. Elliott, Muntaser E. Ibrahim, Heyam S. Ali, Christian C. Wales, Ibrahim Nourwali, Ahmed N. Aljarbou, Adil H. H. Bashir, and et al. 2020. "The Interplay of Dysregulated pH and Electrolyte Imbalance in Cancer" Cancers 12, no. 4: 898. https://doi.org/10.3390/cancers12040898
APA StyleAlfarouk, K. O., Ahmed, S. B. M., Ahmed, A., Elliott, R. L., Ibrahim, M. E., Ali, H. S., Wales, C. C., Nourwali, I., Aljarbou, A. N., Bashir, A. H. H., Alhoufie, S. T. S., Alqahtani, S. S., Cardone, R. A., Fais, S., Harguindey, S., & Reshkin, S. J. (2020). The Interplay of Dysregulated pH and Electrolyte Imbalance in Cancer. Cancers, 12(4), 898. https://doi.org/10.3390/cancers12040898