Blocking these two enzymes could make cancer cells mortal
Washington D.C. [U.S.A.], May 17 : Scientists have found two specific antioxidant enzymes that are linked to making cancer cells mortal.According to a study conducted by the Ecole Polytechnique Federale De Lausanne, PRDX1 and MTH1 have the ability to shun the cancer cells completely.
Before cell division, the long strings of the cell's DNA are wrapped tightly into the structures we know as chromosomes. This protects the cell's genetic material from physical and chemical damage.
The ends of chromosomes are called telomeres. These are specialised structures that have to be replicated with each cell division cycle. But the complete replication of telomeres up to the very ends of chromosomes also requires specialized mechanisms, and these are limited.
Telomeres are also very sensitive to oxidative damage, which affects their ability to replicate. Because of this, telomeres shrink over time, limiting the lifespan of cells. Telomere shortening is essentially the cause of cell aging.
Now, researchers Joachim Lingner and Wareed Ahmed have discovered the two antioxidant enzymes - PRDX1 and MTH1 - that work together to prevent oxidation of telomeric DNA at chromosome ends.
The scientists disrupted both the enzymes in cancer cells and found that the cells' telomeres shrunk with every round of cell division, eventually disappearing altogether.
One of the promising targets in cancer therapy is the enzyme telomerase. Normally, telomerase prevents telomeres from shortening in germ and stem cells, which helps with development.
But telomerase is also highly active in cancer cells, keeping their telomeres intact and making the cells virtually immortal. The new work shows that disrupting PRDX1 and MTH1 prevents telomerase from counteracting telomere shortening.
So far, attempts to efficiently block telomerase in cancer have not been fruitful in the clinic. The discovery of the co-operating enzymes opens up a new opportunity to indirectly block telomerase. "Instead of inhibiting the enzyme itself, we target its substrate - the chromosome end - making it un-extendable by telomerase," said Lingner.
The study appears in the journal Genes and Development.