Why is 3-Bromopyruvate (3-BP) more beneficial than other metabolic inhibitors like dichloroacetic acid (DCA) or 2-Deoxyglucose (2DOG) in killing cancer cells?

The answer below is based on experimental data in vitro.

As a small molecule inhibitor, all three molecules above can target the energy production pathways in cancer cells. However, 3-BP is more effective and beneficial for the following reasons.

First, 3-BP is less toxic and more effective than DCA and 2DOG due to its preferential entry into cancer cells and its capacity to target simultaneously the two major energy production pathways (glycolysis and mitochondrial oxidative phosphorylation).

DCA and 2DOG are more cytotoxic because they enter both normal healthy and cancerous cells. Their chemical structures do not provide for specificity to cancer cells. In fact, they enter more normal cells than cancer cells and harm normal cellular functions.

Secondly, DCA and 2DOG are less effective than 3-BP in killing cancer cells because each agent targets primarily only one of a cell’s two energy production pathways, thus allowing such cells to rely on the other pathway for survival. For example, 2DOG will slow down only the glycolytic pathway but not mitochondrial function. Consequently, cancer cells will thrive utilizing mitochondrial functions.

DCA improves mitochondrial function but not the glycolytic energy production pathway. Unlike 2DOG and DCA, 3-BP while leaving normal cells unharmed will destroy both energy production pathways of cancer cells upon its preferential entry via monocarboxylate transporters (MCTs). That is why 3-BP is much more effective than DCA and 2DOG while exhibiting little to no toxicity.

“Patients should be warned about the dangers of chemotherapy after research showed that cancer drugs are killing up to 50 percent of patients in some hospitals. For the first time, researchers looked at the numbers of cancer patients who died within 30 days of starting chemotherapy, which indicates that the medication is the cause of death, rather than the cancer.” There are serious effects from chemotherapy as seen in an August 2016 article by Sarah Knapton, Science editor of The Telegraph.

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