Mitochondria and glycolysis

As mentioned in a previous post the acquisition of the glycolytic metabolism is regarded by many researchers as a necessary step on the carcinogenic path (this is known as Warburg effect). Compared to healthy cells, glycolytic cells do no need oxygen for their metabolism and although this is very inefficient it has advantages such as the capability of surviving in environments that do not have vasculature in the vicinity and the capability of acidifying the environment (which makes other cells go to programmed death and leaves glycolytic cells room to grow). The reason that healthy cells have a more efficient metabolism is due to the mitochondria, the cellular organelles that oxidises sugar molecules to produce energy. Mitochondrias are what remains of symbiotic bacteria that in the last couple of thousands of millions of years have became integral parts of the cells of many living beings. Glycolytic cells seem to revert to a premitochondrial state thus forfeiting the need of oxygen.

Researchers at the university of Harvard Medical School have created a method based on RNAi (RNA interference, the revolutionary method to knock out genes using double stranded RNA which was the work that has rewarded its authors the Nobel prize in medicine in 2006) in order to put the mitochondria back to work not with the purpose of normalising the metabolism of tumour cells but for the role they play in programmed cell death. The result of applying this therapy on animals resulted in a surge of tumour cells performing apoptosis and a significant increase in the survival rate.

Mitochondria and apoptosis

A couple of posts ago I mentioned this research in which RNAi was used to restore the functionality of the mitochondria, especially its role in apoptosis. Now I read that the same results are being obtained by Dr. Michelakis and colleagues at the University of Alberta in Canada using a well known drug, dichloroacetate (DCA).

DCA is an affordable drug that has been previously used to treat metabolic disorders so it is known to be safe and has no patent. What should have been a blessing could also be a curse since there is little incentive to large pharmaceutical companies to finance the clinical trials. The news has been reported in all sorts of news outlets from Cancer Cell to Slashdot and including The Economist. In this website you will be able to find the latest results as well as information on how to donate money so Dr. Michelakis and his group can finance the clinical trials.

Incidentally, in the link pointing to these news in the online version of The New Scientist, a researchers from Dundee mentions something I did not think of at that time. It could be that the metabolism and not genetic mutations spark cancer. Of course for the metabolic switch to take place you will still need hypoxia (low oxygen due to distance to vasculature) which means, if I am not wrong, a neoplasm.