The pH level in cells regulates the growth and development of normal cells as well as tumor cells. The pH balance is aided by proteins which carry acid and bases in and out of cells. If carbon dioxide and lactic acid build up in cells due to rapid metabolism, the cells become acidified and growth is impaired. For cancers to progress, they must import bicarbonate to alkalinize.
The proteins which remove hydrogen ions (acid) from cells are in normal cells, as well as in increased numbers in cancer cells. The process of acid removal is called acid extrusion, and bicarbonate importers can have the same result (alkalinization) by being transported into cells resulting in production of carbon dioxide. Carbonic anhydrase enzymes help maintain balance between carbon dioxide, bicarbonate and hydrogen, thereby facilitating the conversion between carbon dioxide and bicarbonate.
Five different cancers were reviewed in this study, and the cells were examined as clusters (spheroids). The rate of pH change within cells varied in different cancers. The tissue intracellular pH regulation is very dependent on adequate bicarbonate transport into cells, even more so than on proton (hydrogen ion) export for pH balance.
Carbon dioxide and bicarbonate have been shown to be important to the ability of cells to extrude acid from cells. Tumor cells must have good pH control for rapid growth, and they must handle large amounts of acid load produced by rapid metabolism. This is important even in parts of tumors with poor circulation which are more acidic. Solid tumors must survive in spite of an acid core in the presence of a need to maintain an alkaline environment inside the cells.
Increasing the extracellular bicarbonate has been proposed as a way to treat cancers. This could fail due to the effect of bicarbonate being supportive of better pH control and survival of cancer cells. The proteins in cell walls, which are important for carbon dioxide/bicarbonate transport, may be better targets for cancer therapy.
CONCLUSION: The cellular balance of carbon dioxide and bicarbonate is important in cancer cells, and the presence of carbonic anhydrase enzymes improves that balance. Protein in cell walls improves the transport of bicarbonate into cells. These are possible targets for use in cancer therapy.
NOTE: pH is a measure of acidity or alkalinity based on a formula. A pH below 7.0 is acid, while a pH above 7.0 is alkaline.
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