15 August 2012

A new drug against cancer and age-related diseases

An international group of researchers working under the leadership of Igor Roninson from the University of South Carolina has developed a new type of drugs that can help in the fight against cancer and age-related diseases.

In 2000, Robinson and his colleagues published in the Proceedings of the National Academy of Sciences the results of work indicating that the p21 protein is able to activate many genes involved in the mechanisms of cancer and other pathologies associated with old age, including Alzheimer's disease and arthritis. These unfavorable changes for the body are most pronounced in cells that have entered the phase of physiological aging. Physiological aging is a natural outcome of the cell's existence, but it can occur prematurely as a result of damage caused by exposure to various factors, such as chemo- and radiotherapy used to treat cancer.

After this discovery, Robinson fully devoted his work to deciphering the mechanisms triggered by the p21 protein and developing drugs that can protect cells that have entered the phase of physiological aging from their influence in various diseases.

The gene expressing p21 is activated in damaged cells, which leads to the synthesis of a protein that stops the division of these cells by binding enzymes of cyclin-dependent protein kinases (CDK). The results of the latest work indicate that the pathogenic effects of p21, at least in part, are due to its interaction with one of the representatives of this class of enzymes – CDK8. This protein kinase controls the activity of many different genes, but does not affect the process of cell division. Protein p21 inhibits the activity of most cyclin-dependent protein kinases, but stimulates the activity of CDK8, which, in turn, activates the expression of a number of genes.

Under Robinson's leadership, the specialists of the company Senex Biotechnology founded by him have developed a new class of drugs that inhibit CDK8. They also demonstrated that these drugs can overcome some of the most unpleasant aspects of the use of chemotherapy.

Chemotherapy can reduce the size of some tumors or even completely destroy them, but it damages normal tissues of the body. Among other undesirable side effects, anticancer drugs stimulate the production of molecules by damaged cells that activate the growth and spread of tumor cells, as well as their acquisition of resistance to treatment.

This effect was demonstrated in healthy mice that underwent chemotherapy, after recovery from which they were injected with malignant cells. Compared with animals of the control group, tumors formed significantly more often and faster in mice that underwent chemotherapy. Moreover, the blood of the experimental group of mice contained a large amount of proteins that stimulate the growth of tumor cells.

However, the administration of Senexin A (Senexin A) to animals – a synthetic CDK8 inhibitor developed by Robinson's group – blocked the effect of chemotherapy stimulating tumor growth. This drug also increased the effectiveness of an antitumor drug administered to animals with malignant tumors.

The mechanism of action of the CDK8 inhibitor is to stop the synthesis of toxic proteins by cells that have entered the phase of physiological aging. The drug does not reverse the process of cell aging itself, which is a natural program to prevent malignant cell degeneration. Thus, the development of this drug gives rise to a new pharmacological approach to the treatment of cancer and possibly other age-related diseases such as Alzheimer's disease, atherosclerosis and arthritis.

Article by D. C. Porter et al. Cyclin-dependent kinase 8 mediates chemotherapy-induced tumor-promoting paracrine activities published in the journal Proceedings of the National Academy of Sciences.

Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of ScienceDaily:
New Class of Drugs May Affect Cancer and Aging.


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