Scientists have discovered a link between sirtuin-3 levels and the sensitivity of cancer cells to mitocans

Brief retelling from RIA II

Russian scientists, together with foreign colleagues, discovered that the sensitivity of a cancer tumor to mitocan drugs depends on the amount of the sirtuin-3 protein.

During the experiments, it was found that cells with high levels of sirtuin-3 are resistant to mitocans, and cells with low levels of this protein are sensitive to the drugs.

Further research into the phenomenon is planned to develop personalized treatment strategies for certain types of cancer.

MOSCOW, October 5 - RIA Novosti. Russian scientists became involved in the discovery of a protein molecule, the quantity of which can be used to predict whether a cancer tumor will be sensitive to the action of drugs from the so-called mitocans, and to determine in advance which treatment option will bring maximum benefit to a particular patient, the Russian Science Foundation (RSF) told RIA Novosti.

One way to destroy cancer cells is to disrupt the functioning of their “energy stations” - mitochondria. But mitocane drugs do not work in some tumors. The reason for this selectivity remained unclear for a long time.

Scientists from the Institute of Molecular Biology named after V.A. Engelhardt RAS (IMB, Moscow), Moscow State University named after M.V. Lomonosov and the Karolinska Institute (Sweden) have found a molecule on which the sensitivity of the tumor to mitocan drugs depends. It turned out to be sirtuin-3, a protein that is located in mitochondria and protects cells from oxidative stress.

Researchers within the framework of a project supported by a grant from the Russian Science Foundation conducted experiments with lung, ovarian and neuroblastoma (malignant brain tumor) cancer cells. In dozens of laboratory cell lines, the authors measured the level of sirtuin-3 protein and selected variants with both initially high and initially low levels of this protein. The scientists added an antitumor drug from the mitocan class to all selected cells.

Cells that had a lot of sirtuin-3 were resistant to mitocan, and cells with low levels of this protein died from this drug. “To test whether it was really sirtuin-3, and not other differences between cell lines, the researchers artificially changed the levels of this protein in cells. To do this, lines with low sirtuin-3 (sensitive to mitocan) were forced to produce the protein in excess, and in cells with a high initial level of sirtuin-3 (unresponsive to the drug) they suppressed its synthesis,” noted the RSF.

The connection between the amount of sirtuin-3 and the sensitivity of cells to mitocan was confirmed: when the amount of sirtuin-3 was reduced in drug-resistant cells, they became sensitive to therapy and died. Conversely, when sirtuin-3 became abundant in initially sensitive cells, they became resistant to the drug.

“This effect is explained by the fact that mitocans cause oxidative stress in cells, disrupting the functioning of mitochondria. When there is a lot of sirtuin-3, it protects tumor cells, helping them cope with aggressive forms of oxygen and avoid death. This observation will allow us to assess in advance whether this or that type of therapy will be effective for each specific patient,” said Maria Yapryntseva, a participant in the project supported by a grant from the Russian Science Foundation, an employee of the laboratory of mechanisms of cell death at the IMB.