DCA treatment of cancer by inducing apoptosis

Scientists cure cancer but no one takes notice

Canadian scientists (metabolic modulation of glioblastoma with dichloroacetate) tested this dichloroacetate (DCA) on human's cells; it killed lung, breast and brain cancer cells and left the healthy cells alone. It was tested on Rats inflicted with severe tumors; their cells shrank when they were fed with water supplemented with DCA. The drug is widely available and the technique is easy to use, why the major drug companies are not involved? Or the Media interested in this find? 

Cheap, 'safe' drug kills most cancers

It sounds almost too good to be true: a cheap and simple drug that kills almost all cancers by switching off their "immortality". The drug, dichloroacetate (DCA), has already been used for years to treat rare metabolic disorders and so is known to be relatively safe.

DCA attacks a unique feature of cancer cells: the fact that they make their energy throughout the main body of the cell, rather than in distinct organelles called mitochondria. This process, called glycolysis, is inefficient and uses up vast amounts of sugar.

Until now it had been assumed that cancer cells used glycolysis because their mitochondria were irreparably damaged. However, Michelakis's experiments prove this is not the case, because DCA reawakened the mitochondria in cancer cells. The cells then withered and died (Cancer Cell, DOI: 10.1016/j.ccr.2006.10.020).

Michelakis suggests that the switch to glycolysis as an energy source occurs when cells in the middle of an abnormal but benign lump don't get enough oxygen for their mitochondria to work properly. In order to survive, they switch off their mitochondria and start producing energy through glycolysis.

Crucially, though, mitochondria do another job in cells: they activate apoptosis, the process by which abnormal cells self-destruct. When cells switch mitochondria off, they become "immortal", outliving other cells in the tumour and so becoming dominant. Once reawakened by DCA, mitochondria reactivate apoptosis and order the abnormal cells to die.

"The results are intriguing because they point to a critical role that mitochondria play: they impart a unique trait to cancer cells that can be exploited for cancer therapy," says Dario Altieri, director of the University of Massachusetts Cancer Center in Worcester.

The phenomenon might also explain how secondary cancers form. Glycolysis generates lactic acid, which can break down the collagen matrix holding cells together. This means abnormal cells can be released and float to other parts of the body, where they seed new tumours.

Cancer cell

Cancer progression and its resistance to treatment depend, at least in part, on suppression of apoptosis. Although mitochondria are recognized as regulators of apoptosis. In 1930, Warburg suggested that mitochondrial dysfunction in cancer results in a characteristic metabolic phenotype, that is, aerobic glycolysis (Warburg, 1930).

picture courtesy:http://www.sott.net/article/
228583-Scientists-cure-cancer-but-no-one-takes-notice  

Positron emission tomography (PET) imaging has now confirmed that most malignant tumors have increased glucose uptake and metabolism. This bioenergetic feature is a good marker of cancer but has not been therapeutically pursued, as it is thought to be a result and not a cause of cancer; that is, the cells rely mostly on glycolysis for energy production because of permanent mitochondrial damage, preventing oxidative phosphorylation. However, whether the mitochondria in cancer are indeed damaged and whether this is reversible remain unknown. (http://www.sciencedirect.com/science/article/pii/S1535610806003722)

Cancer mitochondria are hyperpolarized and have suppressed oxidative metabolism, both of which are reversed by DCA

The small molecule DCA is a metabolic modulator that has been used in humans for decades in the treatment of lactic acidosis and inherited mitochondrial diseases. Without affecting normal cells DCA reverses the metabolic-electrical remodeling, inducing apoptosis and decreasing tumor growth. 

picture courtesy:http://www.sciencedirect.com/
science/article/pii/S1535610806003722  

DCA in the drinking water at clinically relevant doses for up to 3 months prevents and reverses tumor growth in vivo, without apparent toxicity and without affecting hemoglobin, transaminases, or creatinine levels. The ease of delivery, selectivity, and effectiveness make DCA an attractive candidate for proapoptotic cancer therapy which can be rapidly translated into phase II-III clinical trials. (http://www.sciencedirect.com/science/article/pii/S1535610806003722)

Paul Clarke, a cancer cell biologist at the University of Dundee in the UK, says the findings challenge the current assumption that mutations, not metabolism, spark off cancers. "The question is: which comes first?" he says.

Note:Text and pictures were thankfully shared from their original sources as listed below:

http://www.sott.net/article/228583-Scientists-cure-cancer-but-no-one-takes-notice

http://stm.sciencemag.org/content/2/31/31ra34.abstract

http://www.newscientist.com/article/dn10971-cheap-safe-drug-kills-most-cancers.html#.U2MTU5Fb2Sq

http://www.sciencedirect.com/science/article/pii/S1535610806003722