Mitochondria generate most of the chemical energy needed to power the cell's biochemical reactions. As such, they are known as the cell's powerhouse.
In recent years, it has been discovered that cancer stem cells are highly dependent on these organelles. So far, however, drugs that target mitochondrial functions have been very toxic.
Now, an international team of researchers from the Max Planck Institute for Biology of Ageing in Cologne, the Karolinska Institute in Stockholm, and the University of Gothenburg has found a tolerable way to target the mitochondria, essentially starving cancer cells.
“We managed to establish a potential cancer drug that targets mitochondrial function without severe side effects and without harming healthy cells”, explained in a statement Nina Bonekamp, one of the lead authors of the study.
Mitochondria have their own genetic material (mtDNA) whose expression is controlled by a set of proteins, one of which is the enzyme mitochondrial RNA polymerase (POLRMT). This particular enzyme is the key to the team's new discovery.
“Previous findings of our group have shown that rapidly proliferating cells, such as embryonic cells, are very sensitive to inhibition of mtDNA expression, whereas differentiated tissues such as skeletal muscle can tolerate this condition for a surprisingly long time. We reasoned that POLRMT as a key regulator of mtDNA expression might provide a promising target”, said Nils-Göran Larsson, head of the research team.
The team then engineered a chemical compound that inhibits POLRMT. This compound was found to decrease tumor growth in mice while being well-tolerated.
“Our data suggest that we basically starve cancer cells into dying without large toxic side effects, at least for a certain amount of time. This provides us with a potential window of opportunity for treatment of cancer”, added Bonekamp. The inhibitor can also be used to further understand the cellular effects of mitochondrial dysfunction.