How to kill a cancer cell? 5 January 2009

Two years have passed since the seminal workof Canadian researchers on a drug that destroys cancer cells while leaving healthy tissue undamaged.
The substance is called DCA (dichloroacetic acid) and is used in the form of sodium salt NaDCA dissolved in water.

The drug is today in second stage of clinical trials (human patients) conducted in University of Alberta, Canada. The official DCA website is located here.

Oprócz oczywistej szansy ratowania ludzkiego życia badanie te oferują interesujące wyjaśnienie sposobu działania raka. Uczeni sugerują, że większość raków nie jest chorobą o podłożu genetycznym ale raczej metabolicznym. I to taką, na którą lekarstwo wymyślono i używano już dawno, ze znanymi skutkami ubocznymi.
Aby docenić prostotę pomysłu należy poznać kilka szczegółów oddychania komórkowego.

Każda żywa komórka w naszych ciałach potrzebuje energii do podtrzymywania czynności życiowych. Energia ta pochodzi ze strawionego pożywienia, które do komórek dociera w postaci cząsteczek glukozy. W procesie oddychania komórkowego energia zmagazynowana w wiązaniach chemicznych glukozy jest przenoszona do cząsteczek ATP (adenozyno-tri-fostoran).

Besides its considerable potential as a life saver DCA has also a scientific appeal because it offers a single explanation of inner workings of many distinct cancers. Namely, it suggests that cancer is a metabolic disease rather than genetic.
To appreciate that point let position it in the large picture of cellular respiration.

Each living cell in our bodies needs to produce energy in a form suitable to fuel necessary biochemical reactions. The process of energy conversion is called a cellular respiration and the goal is to store energy in ATP molecules.
The original energy comes from digested food that reaches cells in the form of glucose molecules and here the respiration starts.

The respiration in many cancer cells stops on glycolysis because their mitochondria are disabled due to the inhibition of mitochondrial gate-keeping enzyme pyruvate dehydrogenase (PDH). Glycolysis is less efficient in energy production than mitochondria-based glucose oxidation and a cell must use up more glucose to sustain its live. This higher glucose uptake is actually exploited in positron emission tomography with fluorodeoxyglucose (FDG-PET) that is routinely used for cancer detection.

Disabled mitochondria have hyperpolarized inner membrane and this electrostatic potential build up keeps cell’s apoptotic agents confined to mitochondria and cell ability to commit suicide is impaired. Some cancer cells become biologically immortal.

The DCA activates the PDH enzyme, thus mitochondria are revived, their membrane polarization normalizes and cell apoptotic mechanisms are restored.
In healty cells, no changes are detected under DCA treatment.

The experimental technique of the DCA function consists on monitoring the mitochondrial membrane polarization. Cultures of cancer cells are stained and observed under a confocal microscope. After about 5-10 min of NaDCA application the mitochondrial polarization returns to normal and cancer cells undergo apoptosis while nothing happens to normal cells.

The supplemental information on the experimental issues is stored here. If you have an access to a confocal microscope and would like to contribute to this research, please, contact us

Update December 1, 2010:
Currently, we have started an experiment that will test if sarcoma cells are vulnerable to the DCA treatment.

Zbigniew Karkuszewski, January 5-th 2009