Intracellular and extracellular pH levels are manipulated by the cancer process to promote cancer growth. Our ability to manipulate those pH levels may be useful in cancer treatment. Potential approaches include the following: (1) Alkalinizing therapy to increase extracellular pH. (2) Proton pump inhibitors to reduce the intracellular space toward acidity. (3) Rapid intracellular acidification to kill the cancer cell. (4) Rapid extracellular acidification to release specially designed drugs.
Because of the rapid production of lactic acid by cancer cells, the extracellular space in cancers becomes slightly acidic. Intracellular pH is usually normal due to buffers and proton pumps, which pump protons outside the cells. Tumor pH reduction (acidity) correlates with poor tumor prognosis. Tumor acidity correlates with tumor invasiveness, metastases, angiogenesis, and chemoresistance.
Returning the extracellular pH to normal may be beneficial. Systemic buffering with such things as bicarbonate or trisodium citrate increases extracellular pH (alkalinizes.) Mice which had been implanted with tumors were treated with sodium bicarbonate. The primary tumors were not changed by the alkalinization, but, there was a reduction in size and numbers of metastases.
Alkalinization of the extracellular space can be from a low protein diet, with high potassium-rich fruits, vegetables, and juices. Alkaline diets have long been recommended by naturopaths to slow cancer growth. Oral use of sodium bicarbonate increases the alkalinity. The Whitaker Wellness Institute uses alkalinizing therapy in cancer patients.
Proton pump inhibitors (PPIs) block the cell wall ion pumps that create the alkaline interior by releasing protons to the extracellular spaces. There are several forms of Na+/H+ exchangers (NHE) to pump protons out of cells. Cancers produce extracellular carbonic anhydrase enzyme to acidify the extracellular space, producing bicarbonate to be returned into cells.
PPIs reduce the intracellular pH and raise the extracellular pH. Intracellular acidification reduces cancer proliferation and increases apoptosis (natural cell death) in certain cancer types. Increasing intracellular acidity increases cell death in the presence of hyperthermia. A large increase in acidity can increase apoptosis of cancer cells and can promote the activity of certain cancer drugs that are pH sensitive.
PPIs are used to reduce gastric acid production. PPIs suppress human melanoma cancer tissue grafted on mice and doubling their survival time. NHE1 pumps also mediate proton extrusion.
The process of tumor acidification can be improved by increasing the rate of tumor glycolysis. Glycolysis is low in tumors due to poor tumor circulation. Hyperglycemia has been shown to boost glycolysis in tumors and reduce extracellular pH. Hyperacidification of cancer extracellular spaces is being studied through the use of medications.
CONCLUSION: Extracellular hyperacidity of tumors increases tumor spread, helps tumors resist cancer drugs, and protects them from immune attack. There is evidence that sodium bicarbonate therapy reduces that acidity. Proton pump inhibitors can further alter that acidity.
Intracellular acidification promotes tumor apoptosis. This approach can be maximized by hyperglycemia to increase glycolysis. The Warburg phenomenon was proposed long ago that tumors acidify. Perhaps, it will prove to be therapeutic to treat that acidity.
NOTE: Read more about Otto Warburg and the Warburg phenomenon.
Resveratrol and quercetin are natural PPIs. There are natural carbonic anhydrase inhibitors, too. Read about carbonic anhydrase inhibitors for cancer treatment.
Systemic alkalizers include the following: Potassium citrate, citric acid, tricitrates, and sodium citrate.