CLINICAL TRIALS OF DCA AGAINST CANCER TUMORS AND THE UNIVERSITY OF ALBERTA USES THE WARBURG EFFECT
Does DCA, dichloroacetate acid kill cancer cells? E D Michelakis etal have published a new paper in the British Journal of Cancer about dichloroacetate and cancer. A while back dichloroacetate was all over the news. I wrote in Purple Medical Blog that it was being studied by scientists at the University of Alberta. On the web, DCA dichloroacetate was being touted by some especially in the news as a possible drug for use against cancer. You may remember that DCA is a generic chemical that scientists theorized might be able to suppress tumor growth. A web site that sold DCA was ordered shut down by the FDA.
It can be toxic and in any event the scientists said that the commercially available product was not appropriate for use. The conspiracy theorists suggested that since it was generic and non patentable the "big boys" in the drug industry had no interest in it. Glenn Beck, the headline news personality even vented about it on his tv show. (See the video) But I haven't heard much lately. Indeed DCA seemed to have fallen off the radar, news wise. Or perhaps not. E D Michelakis etal have published a new paper in the British Journal of Cancer called Dichloroacetate (DCA) as a Potential Metabolic-Targeting Therapy for Cancer. Michelakis in the article writes "The unique metabolism of most solid tumours (aerobic glycolysis, i.e., Warburg effect) is not only the basis of diagnosing cancer with metabolic imaging but might also be associated with the resistance to apoptosis (cell self destruction) that characterizes cancer.
How does dca work on cancer? It is supposed to restore the normal energy function of the cells and the ability of cells to undergo programmed cell death called apoptosis. Cancer cells seem to be able to avoid apoptosis. The cells in our bodies contain little energy factories called mitochondria. The factories can employ different chemical processes to produce energy depending on the outside conditions. Namely is oxygen available or not? The Alberta scientists say "The generic drug dichloroacetate is a small molecule that, by inhibiting a chemical called pyruvate dehydrogenase kinase increases the (flow) of pyruvate into the mitochondria, promoting the process glucose oxidation over glycolysis" and apoptosis. Normal cells usually use a biological process called oxidative phosphorylation when oxygen is available and only switch over to another process called anaerobic (without oxygen) glycolysis in conditions of low or no oxygen (anaerobic conditions).
As the doctor at the Respectful Insolence blog points out "The entire concept behind the use of DCA is to target a phenomenon known as the Warburg Effect...This effect was first observed by a biochemist named Otto Warburg back in the late 1920's in tumor cells...Dr. Warburg postulated that in tumor cells the mitochondria (which is where oxidative phosphorylation takes place) are reduced or functionally impaired. Indeed, he postulated more than that, namely that impaired mitochondrial function contributes to tumorigenesis.(having to do with malfunctioning of the energy factories of the cell called mitochondria and the failure of cancer cells to undergo normal cell death). The problem in normal cells is that glycolysis produces much less usable chemical energy per molecule of glucose (sugar) than oxidative phosphorylation, and normal cells normally cannot survive on anaerobic glycolysis alone for very long. However, many tumor cells can. Indeed, many tumor cells continue to use glycolysis and produce lactate even in aerobic conditions, an observation that led Dr. Warburg to postulate that in tumor cells the (energy producing regions called) mitochondria (which is where oxidative phosphorylation takes place) are reduced or functionally impaired".
Michelakis in the article writes "The unique metabolism of most solid tumours (aerobic glycolysis, i.e., Warburg effect) is not only the basis of diagnosing cancer with metabolic imaging but might also be associated with the resistance to apoptosis (cell self destruction) that characterizes cancer. The glycolytic phenotype in cancer appears to be the common denominator of diverse molecular abnormalities in cancer and may be associated with a (potentially reversible) suppression of mitochondrial function. The generic drug dichloroacetate is an orally available small molecule that, by inhibiting the pyruvate dehydrogenase kinase, increases the flux of pyruvate into the mitochondria, promoting glucose oxidation over glycolysis. This reverses the suppressed mitochondrial apoptosis in cancer and results in suppression of tumour growth in vitro and in vivo. Here, we review the scientific and clinical rationale supporting the rapid translation of this promising metabolic modulator in early-phase cancer clinical trials".