A new drug destroys cancer cells by invading mitochondria

Newly developed fertilizers injure cancer cells by invading their “power centers” – the so-called mitochondria. The new fertilizer prevents the genetic information inside mitochondria from being read. Researchers from the Max Planck Institute for Aging Biology in Cologne, the Karolinska Institute in Stockholm and the University of Gothenburg report in their study that this fertilizer could be used as an anti-tumor drug in the future ; not only in mice but also in human patients.

Mitochondria provide our cells with energy and cell building blocks that are essential for the normal functioning of tissues and organs. For a long time, it was assumed that cancer cell growth was independent of mitochondrial function. However, this long-standing dogma has been challenged in recent years. In particular cancer stem cells are highly dependent on mitochondrial metabolism. Because of the primary role of mitochondria for normal mammary function, and because drugs that target mitochondrial activity are highly toxic, it has so far been difficult to target mitochondria for the treatment of cancer.

Now an international team of researchers has found a way to overcome these problems. “We were able to establish a cancer drug that can target mitochondrial activity without side effects and without harming healthy cells,” explained Nina Bonekamp, ​​one of the study’s lead authors.

Mitochondria have their own genetic material, the mitochondrial DNA molecules (mtDNA), whose gene expression is mediated by a specific set of proteins. One such protein is the enzyme “mitochondrial RNA polymerase”, abbreviated to POLRMT.

Previous findings of our group have shown that rapidly depleting cells, such as progenitor cells, are highly sensitive to mtDNA inhibition, but different differences such as skeletal muscle may condition them suffer this for an incredibly long time. We reasoned that POLRMT as a key regulator of mtDNA expression could provide a promising target. “

Nils-Göran Larsson, Head of the research team

Fertilizers inhibit mitochondrial RNA polymerase

In collaboration with the Lead Discovery Center, a drug discovery translation group founded by Max Planck Innovation, the research team designed a high-throughput test method for the identification of chemical fertilizers that inhibit POLRMT. The POLRMT inhibitor strongly reduced cancer cell viability and tumor growth in tumor-bearing mice, but was generally well tolerated by the animals.

“Our data suggest that we are basically injuring cancer cells to die without major toxic side effects, at least for a certain amount of time. This gives us a chance that could to treat cancer, “says Nina Bonekamp. “Another benefit of our inhibitor is that we know exactly where it binds to POLRMT and what it does to the protein. This is compared to some other drugs that are even in clinical use . ”With the help of ACUS Laboratories in Cologne and the Max Planck Institute for Biophysical Chemistry in Göttingen, the team identified the chemical binding site of the inhibitor and obtained structural information of the POLRMT-Inhibitor center.

Bonekamp and Larsson agree that it was an interesting journey to translate basic results into a potential drug. They are all excited about the opportunities that their results will open up.

“Because mitochondrial metabolism plays a central role within the cell, I am convinced that our defender of mitochondrial gene expression can be used as a tool in a number of different areas,” explains Bonekamp. “Of course, it is interesting to pursue the potential as an anti – cancer drug, but also as a combined model to further understand the cellular effects of mitochondrial dysfunction and mitochondrial disease.”