Reversal of the normal movements of protons across cell walls seems to underlie all cancer development. The reversal of the normal pH balance across the cancer cell walls results in an intracellular alkalosis with high pH and an extracellular acidosis with low pH. The reversal of the proton gradient across the cell wall, seen only in malignant cells, is an early event in cancer.
Extracellular acidosis induces angiogenesis (growth of new blood vessels,) necessary for cancer growth. A reversal of the normal proton gradient across the cell wall results in an increase in vascular endothelial growth factor (VEGF.) Normal cells die from the extracellular acidification.
The abnormal pH gradient is the result of an increase in many “proton export mechanisms” or proton pumps. Treatment to block proton transport out of the cell may be useful in cancer therapy. Sometimes, as in breast cancer, more than one transport system must be inhibited to cause apoptosis (death of the abnormal cell.) The low intracellular pH induced by proton pump inhibitors (PPIs) in cancer cells induces apoptosis of the cancer cells. Normal cells are less sensitive.
One proton pump is the Na+/H+ exchanger isoform 1 (NHE-1.) NHE-1 inhibition of cells results in severe lowering of the intracellular pH of cancer cells beyond a pH at which cancer cells can survive. Normal cells are very little changed.
Resveratrol and quercetin are PPIs. The monocarboxilate transporter (MCT) can be inhibited by lonidamine and cinnamate (from cinnamon oil.) High levels of MCT are seen in neuroblastoma cells and melanoma cells at a low extracellular pH. High levels of MCT are a sign of poor prognosis in neuroblastoma. Quercetin and lonimidamide are MCT inhibitors. Resveratrol is an ATP synthase inhibitor which can play a role in proton transport, acidifying the intracellular space and causing cancer cell death.
Chemotherapy can induce apoptosis by inducing intracellular acidosis. The resistance of cancer cells to chemotherapy, multidrug resistance (MDR,) is partly due to the strong cancer cell resistance to intracellular acidification.
Severe acidosis has been reported in “spontaneous regression” of cancers. Metabolic acidosis from mild kidney failure has been reported to “reduce, and even reverse rates of tumor growth and invasion in cancer patients.”
CONCLUSION: An important goal in the treatment of cancer is to block the functions of malignant cells to maintain an alkaline intracellular space, avoid low pH apoptosis and to provide multi-drug resistance by the strongly alkaline pH.
NOTE: Read about proton pump inhibition and the effect on melanomas and tumor acidity.
To read the author’s abstract of the article click on the link to the author’s title of the article above.
PMID: 19528473.
Summary #334.
