Home > Dichloroacetic acid (Molecule of the Month for March 2008 )

Picture of Dichloroacetic acid

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Picture of Dichloroacetic acid

CHCl2C(O)OH

Dichloroacetic acid is an analogue of acetic acid in which two of the three hydrogen atoms of the methyl group have been replaced by chlorine atoms. The sodium and potassium salts and esters of dichloroacetic acid are called dichloroacetates, these salts are under investigation as a possible treatment for cancer. The dichloroacetate ion is produced when dissolved in water. As an acid with a pKa of 1.48, pure dichloroacetic acid is very corrosive and extremely destructive to tissues of the mucous membranes and upper respiratory tract.

Owing to the highly corrosive action of the acid, only the salts of dichloroacetic acid are used therapeutically. The dichloroacetate ion stimulates the activity of the enzyme pyruvate dehydrogenase by inhibiting the enzyme pyruvate dehydrogenase kinase. This property has led to trials of DCA for the treatment of lactic acidosis in humans. Randomized controlled trial of DCA in adults with lactic acidosis found that while DCA lowered blood lactate levels, it had no clinical benefit and did not improve hemodynamics or survival. Thus, while early case reports and pre-clinical data suggested that DCA might be effective for lactic acidosis, subsequent controlled trials have found no clinical benefit of DCA in this setting. In addition, clinical trial subjects were incapable of continuing on DCA as a study medication owing to progressive toxicities.

A study published in January 2007 by researchers at the University of Alberta, testing DCA on in vitro cancer cell lines and a rat model, found that DCA restored damaged mitochondrial function in cancer cells, which restored the mechanism of apoptosis, killing cancer cells in vitro, and shrinking the tumors in the rats. In March 2008, Harvard Medical School identified an enzyme which enables cancer cells to consume the huge quantities of glucose they need to fuel uncontrolled growth. Writing in Nature, they describe how starving cancer cells of the enzyme curbed their growth. The key enzyme, pyruvate kinase, comes in two forms, but the Harvard team found that only one - the PKM2 form - enables cancer cells to consume glucose at an accelerated rate. This recent observation may explain the role of DCA in tumor reduction. However, formal clinical trials of the anti-cancer properties of DCA have yet to report any success in humans. Worryingly at this stage some doctors are prescribing DCA to patients (so called off-label), this could be very dangerous (and even illegal) with such a toxic chloroacetic acid.

Formal Chemical Name (IUPAC)
2,2-dichloroacetic acid

References

http://en.wikipedia.org/wiki/Dichloroacetic_acid

http://news.bbc.co.uk/1/hi/health/7292652.stm

Update by Karl Harrison
(Molecule of the Month for March 2008 )