Throughout life, cells are subjected to different sources of environmental stress, such as solar radiation, which cause defects to accumulate. Upon reaching a certain level of damage, defense mechanisms are activated to prevent a tumor from developing: either the cell performs apoptosis (“commits suicide”), or it enters senescence, a kind of “zombie” state, among life and death, in which despite continuing to be alive, it stops working and, in addition, begins to manufacture products that spread the zombie state to other healthy cells in the surroundings.
While the organism is young, the immune system is in charge of eliminating these cells and cleaning the tissues. Now, as we add years, the immune system stops performing this maintenance task; the reasons for this behavior are unknown. This causes these zombie cells to accumulate in the tissues, which begin to function worse, and age.
Studies carried out with animals have shown that when certain drugs, called senolytics, capable of eliminating these old cells, are administered, it is possible to improve the life expectancy and quality of life of animals.
In this regard, a team made up of, among others, Salvador Macip, from the Open University of Catalonia (UOC) and the University of Leicester in the United Kingdom, as well as Fares Al-Mansour, from the latter institution, has discovered a molecule that could help clean up aging cells left behind after cancer treatments. This molecule, called CUDC-907, destroys old cells quite efficiently and specifically, with few side effects on healthy cells.
Artist’s impression of a “zombie” cell among normal cells. (Illustration: Amazings/NCYT)
“The drug that we have identified destroys old cells in a very powerful way and, in addition, it is already being investigated against some cancers, so it could have a double effect: anti-cancer and, at the same time, anti-old cells that make the cancer come back.” Macip points out.
In cancer, this drug, which works by inhibiting two cell communication pathways (one of these pathways was unknown until now and has been discovered by Macip’s team), was being investigated to eliminate cells that are severely damaged after a chemotherapy or radiation therapy, but they do not die, but instead senescence, which can contribute to the re-growth of a tumor. “This drug could be given in conjunction with chemo or radium to kill these zombie cells and greatly reduce cancer regrowth,” says Macip.
In this work, the researchers have seen, using different models of human cancer cells, that the dual inhibitor CUDC-907 eliminates a specific type of senescent cells with limited side effects.
Now, tests will begin with animal models and, if good results are obtained, they will test it on humans.
The researchers believe that the drug could also be applied in conditions in which the accumulation of senescent cells plays an important role, such as Alzheimer’s disease.
“Perhaps an intensive dose of the drug would cleanse the brain and prevent the disease from progressing. It could also be useful in idiopathic pulmonary fibrosis, to slow its progression, rather than aging itself,” says Macip.
The study is titled “Characterization of the HDAC/PI3K inhibitor CUDC-907 as a novel senolytic”. And it has been published in the academic journal Aging, in the United States. (Source: UOC)