Cancer cells can be aged
Cellular aging is a condition in which cells finally lose the ability to divide. This is a natural defense mechanism that prevents mutated cells from turning into a tumor. The cells sink into a state similar to hibernation. The process is controlled by epigenetic tags located on the DNA sites encoding protein synthesis. Cancer cells have learned to disable these tags, but the mechanism of this process has been unknown until now.
An international team of researchers led by Professor Clemens A. Schmitt from the University of Charite, the Max Delbruck Center for Molecular Medicine in Berlin and the Berlin Institute of Health found that cancer cells remove epigenetic tags with the enzyme demethylase. Genetic or drug inhibition of demethylase triggers an antitumor defense mechanism.
The research team examined nearly 500 tissue samples taken from melanoma patients. Approximately one-third of the samples showed significantly elevated levels of demethylase.
In melanoma cell cultures, as well as in mice and danio rerio fish with melanoma, the researchers genetically suppressed the activity of the enzyme demethylase. They also applied chemical agents to inactivate it. In both cases, the cancer cells plunged into a state similar to hibernation – their division completely stopped.
The experiment was successful even among mouse models with implanted human melanoma cells – this is important for further study of the method in humans.
One of the chemicals used was a new drug for the treatment of lung cancer and blood cancer, which is currently being tested in clinical trials.
In one of the experiments on models with melanoma, immune cells migrated to the tumor after the drug "aging" of cancer cells.
Cellular aging, like apoptosis, is one of the body's defense mechanisms against tumor development. In this case, the genes regulating cell division are suppressed. Methyltransferase enzymes label histones, proteins involved in the packaging of DNA molecules. These tags turn off adjacent sections of DNA.
The ability of demethylase to remove epigenetic tags is crucial in disabling the mechanism of cellular aging.
Cellular aging is an important and promising area of cancer treatment because of its ability to prevent further tumor growth. But its functions are not limited to blocking cancer. Clemens Schmitt believes that the migration of immune cells into the tumor has great potential for the development of a new type of combination therapy. The combined use of demethylase blockers and targeted immunotherapy can be very effective. This is especially true for the treatment of melanoma, since this type of cancer does not respond well to chemotherapy.
Article Y. Yu et al. Targeting the Senescence-Overriding Cooperative Activity of Structurally Unrelated H3K9 Demethylasesin Melanoma is published in the journal Cell.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on MDC materials: Putting black skin cancer to sleep – for good.