3-Bromopyruvate (3-BP): An effective metabolic inhibitor

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In 1931. German physician / scientist Dr. Otto Vanburg, Ph.D., won the Nobel Prize proving that all cancer cells use anaerobic metabolism (they burn sugars without the use of oxygen) to get energy.

The problem is that this mechanism is 18 times less efficient than the aerobic metabolism (which uses oxygen) that normal cells use. Therefore, cancer cells need 18 times more sugar than a normal cell to grow and remain metabolically active.

3-Bromopyruvate research

3-Bromopyruvate

In cancer cells, 3-Bromopyruvate outperforms targeted therapies because targeted therapies quickly become obsolete by intra-tumor heterogenesis (too genetically diverse to have a lasting effect). But 3-BP works on all cancer cells that are positive on a PET scanner.

These cancer cells have a cellular metabolism that can be attacked by a small molecule such as 3-BP. Dr. Peter Pedersen’s laboratory at the hospital Johns Hopkins in Baltimore Maryland examined 3-BP in detail and then formulated 3-BP to improve efficacy, reduce toxicity, and progressively deliver cancer cells.

Patients, scientists and many others are often interested in whether 3-BP is more effective and less toxic to cancer patients than chemotherapy. In fact, 3-BP is one of the most effective anti-cancer drugs , and in some cases, perhaps the most effective. 3-Bromopyruvate targets the energy-producing machinery necessary for cancer cells while leaving the same machinery intact in normal cells.

This discovery was instrumental in launching a new direction in cancer research focused on the selective targeting of energy production factories in mitochondrial cancer cells. In fact, Dr. Peter Pedersen’s lab at Johns Hopkins Hospital is paving the way in conceptualizing and scientifically embracing this new strategy.

Energy and cancer

There are two factories for energy production (ATP) within the cell, i.e. glycolysis and mitochondrial oxidative phosphorylation. In normal cells, about 5 percent of total cellular energy production (ATP) is derived from glycolysis and about 95 percent from mitochondria.

In cancer cells, energy production by glycolysis is significantly increased (up to 60 percent). This dramatic increase in glycolysis in cancer cells results in a significant increase in lactic acid production.

More than 90 percent cancer exhibit this frequent metabolic phenotype. This is the so-called “Warburg effect”, which is a significant increase in glycolysis in cancer cells even in the presence of oxygen. The most commonly used method for detecting cancer clinically, i.e. Positron Emission Topography (PET for short), is based on this metabolic phenotype, i.e. the “Warburg effect”.

Cancer cells that exhibit a “Warburg effect” pump lactic acid produced through a monocarboxylate transporter (MCT). The number of these transporters (considered doors or gates) in cancer cells is much higher than in normal cells.

3-BP lactic acid

3-BP, an analogue of lactic acid, is a small chemical and mimics the chemical structure of lactic acid. Therefore, 3-Bromopyruvate mimics lactic acid can, like a Trojan horse, enter cancer cells via MCT. The effect is weaker on normal cells because they contain very little MCT under normal physiological conditions.

Due to the highly reactive nature of 3-BP, it then neutralizes the two factories producing cancer energy. Cellular energy (ATP) is expended very quickly while 3-Bromopyruvate attacks both factories at the same time causing cancer cells to die (by rupturing the cell membrane). Therefore, when cancer cells are treated with 3-BP, they burst and cell death occurs. Normal metabolic cells remain intact.