Effect of CO2 and lactic acid on intracellular pH of ascites tumor cells

Albers, C.; Kerckhoff, W. van den; Vaupel, Peter; Müller-Klieser, W.

doi:10.1016/0034-5687(81)90011-6

Cited by 17 publications

(12 citation statements)

References 11 publications

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“…19,24 Efficiency of Nonradiative Deactivation of Excited States. Data analysis (Table 2) shows that for both TSPC 4and H 2 TSPC 2internal conversion S 1 f S 0 is the main channel of deactivation. About one-half of the excited TSPC 4molecules deactivate through this channel, as indicated by both the value of Φ IC ) 1 -Φ F -Φ T , and the corresponding rate constant k IC .…”

Section: Resultsmentioning

confidence: 99%

Acid−Base Equilibria in 5,10,15,20-Tetrakis(4-sulfonatophenyl)chlorin: Role of Conformational Flexibility

Kruk¹,

Braslavsky²

2006

J. Phys. Chem. A

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The acid−base equilibria in 5,10,15,20-tetrakis(4-sulfonatophenyl)chlorin were studied in aqueous solution and compared with the respective data for the corresponding porphyrin. The reduction of the pyrrole ring in the tetrapyrrolic macrocycle noticeably influences both free base/monoprotonated and mono-/diprotonated species equilibria. In strong acidic solutions protonation of 4-sulfonatophenyl groups takes place in addition to protonation of the macrocycle core. The photophysical properties of all ionic forms are influenced by an enhanced rate of internal S1 → S0 conversion, leading to about 50% and 90% deactivation through this channel for the free base and diprotonated species, respectively. The enhancement of the rate of the radiationless transitions is explained by an increased conformational flexibility of the chlorin macrocycle with respect to that of a porphyrin. Structural volume change measurements with laser-induced optoacoustic spectroscopy support this explanation. The contraction upon triplet state formation of the free base is about one-half of that measured for the corresponding porphyrin. This contraction should be due to intramolecular structural rearrangements of the macrocycle to adopt a minimum energy conformation in case of the chlorin. On the contrary, for the more rigid porphyrin macrocycle the interactions of the molecule with the solvent environment play a more important role. The diprotonated forms of both porphyrin and chlorin show a high radiationless S1 → S0 conversion rate and seem to have a similar conformational flexibility. In agreement with previous calculations, the conformational flexibility of the diprotonated forms appears to be higher than that of the free base molecule.

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Section: Resultsmentioning

confidence: 99%

Acid−Base Equilibria in 5,10,15,20-Tetrakis(4-sulfonatophenyl)chlorin: Role of Conformational Flexibility

Kruk¹,

Braslavsky²

2006

J. Phys. Chem. A

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“…The studies by Albers et al [9] in 1981 were the first to show that there was an inversion of the pH gradient in malignant tumors. They wrote: "pH i exceeded pH e if either P CO2 and/or the concentration of lactic acid were raised above a critical level".…”

Section: A Short History Of the Ph Paradigmmentioning

confidence: 99%

“…(1) Inhibiting cell cycle progression [247,248], (2) Inducing apoptosis limited to cancer cells [249], (3) Interfering with reactive oxygen species (ROS) metabolism [250], (4) Inhibiting the androgen receptor in prostate cancer [251], (5) Targeting cancer stem cells [252], (6) Downregulating mutant p53 [253] and metalloproteinases 2 and 9 [254], (7) Inhibiting p21-RAS expression [255], (8) Decreasing glycogen synthesis [256], (9) Antagonizing inflammation [257], (10) Inhibiting Hsp 27 [258], (11) Decreasing cMyc and PI3K/Akt signaling [259], (12) Decreasing lipogenesis [260], (13) Amid other anti-cancer effects [261,262].…”

Section: Mct Inhibitorsmentioning

confidence: 99%

Targeting the pH Paradigm at the Bedside: A Practical Approach

Koltai¹

2020

IJMS

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The inversion of the pH gradient in malignant tumors, known as the pH paradigm, is increasingly becoming accepted by the scientific community as a hallmark of cancer. Accumulated evidence shows that this is not simply a metabolic consequence of a dysregulated behavior, but rather an essential process in the physiopathology of accelerated proliferation and invasion. From the over-simplification of increased lactate production as the cause of the paradigm, as initially proposed, basic science researchers have arrived at highly complex and far-reaching knowledge, that substantially modified that initial belief. These new developments show that the paradigm entails a different regulation of membrane transporters, electrolyte exchangers, cellular and membrane enzymes, water trafficking, specialized membrane structures, transcription factors, and metabolic changes that go far beyond fermentative glycolysis. This complex world of dysregulations is still shuttered behind the walls of experimental laboratories and has not yet reached bedside medicine. However, there are many known pharmaceuticals and nutraceuticals that are capable of targeting the pH paradigm. Most of these products are well known, have low toxicity, and are also inexpensive. They need to be repurposed, and this would entail shorter clinical studies and enormous cost savings if we compare them with the time and expense required for the development of a new molecule. Will targeting the pH paradigm solve the “cancer problem”? Absolutely not. However, reversing the pH inversion would strongly enhance standard treatments, rendering them more efficient, and in some cases permitting lower doses of toxic drugs. This article’s goal is to describe how to reverse the pH gradient inversion with existing drugs and nutraceuticals that can easily be used in bedside medicine, without adding toxicity to established treatments. It also aims at increasing awareness among practicing physicians that targeting the pH paradigm would be able to improve the results of standard therapies. Some clinical cases will be presented as well, showing how the pH gradient inversion can be treated at the bedside in a simple manner with repurposed drugs.

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“…5,5-Dimethyl-2,4-oxazolidynedione (DMO) is a weak non-metabolizable organic acid with p K , of 6.13 at 37 "C and acts as a modifier of intracellular pH (Butler, 1953;Waddel and Butler, 1959;Hoffer and Mivech, 1980). DMO distributes between the intracellular and extracellular space.…”

Section: Introductionmentioning

confidence: 99%

“…Changes of DMO concentrations in serum are thus dependent on intracellular pH changes only, DMO should therefore be a sufficient marker of intracellular pH and acid-base balance changes (Waddel and Bates 1969;Albers et al, 1975). Previously described methods for the determination of DMO were based on spectrophotometric measurement, when large doses of DMO were administered (Butler, 1953;Waddel and Butler, 1959), gas-liquid chromatography (Tanaka et al, 1981;Gaidzik and Kmiotek, 1986) or on radioisotope techniques (Saborowski et al, 1973;Tizianello et al, 1977;Albers et al, 1981). Although these isotopic methods for the determination of DMO are very sensitive, they are not practical for most laboratories because of the high cost involved.…”

Section: Introductionmentioning

confidence: 99%

Rapid and simple HPLC determination of 5,5‐dimethyl‐2,4‐oxazolidynedione in rabbit serum

Gaździk

Filipek

Kmiotek

1987

Biomedical Chromatography

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A new method for the determination of 5,5-dimethyl-2,4-oxazolidynedione (DMO) in rabbit serum by reversed phase-HPLC with UV detection is described. The determination of DMO is performed without derivatisation. The internal standard is 5,5-diethylbarbituric acid (barbital). The method is rapid and simple with sensitivity limit of 20 ng/mL, high recovery (above 92%) and is suitable for pharmacokinetic studies.

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Effect of CO2 and lactic acid on intracellular pH of ascites tumor cells

Cited by 17 publications

References 11 publications

Acid−Base Equilibria in 5,10,15,20-Tetrakis(4-sulfonatophenyl)chlorin: Role of Conformational Flexibility

Acid−Base Equilibria in 5,10,15,20-Tetrakis(4-sulfonatophenyl)chlorin: Role of Conformational Flexibility

Targeting the pH Paradigm at the Bedside: A Practical Approach

Rapid and simple HPLC determination of 5,5‐dimethyl‐2,4‐oxazolidynedione in rabbit serum

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