Dichloroacetate or DCA is a small molecule that has been in the press over the last four years due to its potential to inhibit aerobic glycolysis in cancer cells. The cells from each of us usually produce energy in the form of ATP from a variety of nutrient sources plus oxygen using a very efficient process called oxidative phosphorylation.
However, when oxygen is partly depleted, such as in skeletal muscle when exercising strenuously (“going anerobic”), energy is produced from glucose by a far less efficient process called glycolysis. Glycolysis is the most primitive form of cellular metabolism [Note added: This last sentence is not correct; see below for correction from Prof Larry Moran. – APB]
The glycolytic pathway has become of renewed interest in cancer. Why? Because some but not all cancer cells differ from normal cells by using the inefficient production of ATP by glycolysis regardless of the amount of oxygen that’s around. You’ll hear the term “Warburg effect” used to describe this phenomenon because biochemist Otto Warburg published a famous 1956 paper in the journal, Science, suggesting that the origin of cancer lies in the ability of cancer cells to shift metabolism to glycolysis.
In the intervening years, debate has ensued that accelerate glycolysis in cancer cells is just a by-product of the oncogenic process. But we now appreciate that in some cases, the accelerating of glycolysis encourages cancer. For example, the greater level of the enzyme lactate dehydrogenase (LDH) in some cancer cells is now known to be a direct effect of the oncogenic protein, c-Myc, which by itself can cause normal cells to become cancerous.
The unusual nature of some cancer cells to rely on glycolysis even in the presence of oxygen presents an opportunity to possibly target cancer more selectively while minimizing damage to normal cells as occurs with classical chemotherapy drugs or radiation therapy. Indeed, the promise of targeting the Warburg effect in cancer is intoxicating.
At present, there are a few chemicals known to inhibit glycolysis that resemble some of the intermediates in the process but require extremely high concentrations. One is called 3-bromopyruvate – as I wrote here in 2007, this chemical inhibits both glycolysis and oxidative phosphorylation so it would have to be injected directly into the artery that feeds the cancerous tumor. The other chemical is dichloroacetate (DCA).
DCA has been around for a long time and has been used in people with inherited diseases of mitochondrial metabolism. In 2007, a group at the University of Alberta led by cardiologist Evangelos Michelakis demonstrated that very high doses of DCA can slow the progression of human tumor cells grown in immunocompromised rats. The response to this story was unbelievable with internet marketers popping up to sell the simple chemical and conspiracy theorists saying that because DCA was cheap and not patentable, no drug company would ever develop it, it was being kept a secret, and so. In truth, the work was in very, very early stages.
This didn’t stop hopeful patients from seeking out DCA sellers even though DCA can be contaminated with other related substances that are far more toxic. And in the most egregious case among these DCA purveyors, an Edmonton man who purported to sell DCA online was recently arrested in Phoenix and pleaded guilty to five cases of wire fraud – not because he was selling DCA but rather a white powder comprised of some combination of sucrose, lactose, dextran, and starch.
Yes. Not even the unproven DCA. Fake DCA.