An international research group has identified the mechanism responsible for giving the p21 protein its cancer-fighting potency. It is hoped that the findings could advance our ability to target and destroy certain cancer cells.
A research group led by the University of Leicester found that some cancer cells are especially sensitive to a protein called p21. This protein usually causes both normal cells and cancer cells to stop dividing, but it was recently demonstrated that in certain cases it can also kill cancer cells. However, scientists did not understand why p21 was effective at combating these cells.
"If we could harness this 'killing power' that p21 has, we could think of designing new therapies aimed at increasing its levels in tumours," said Dr Salvador Macip, a researcher at the University's Department of Biochemistry. "This is what motivated us to look into it."
In a collaborative effort between the universities of Leicester and Cardiff in the United Kingdom, the University of South Carolina in the United States, and the Karolinska Institutet in Sweden, researchers discovered that cells from sarcomas tended to die in response to p21, and that this was determined by the sensitivity of their mitochondria to oxidants.
"Our research also showed that p21 can kill cells even in the absence of p53, a protein that is in the main responsible for cell death but is inactivated in most cancers," said Dr Macip. "This shows that certain types of cancer, sarcomas for instance, but maybe also others, should respond well to drugs that increase the levels of p21, even if they don't have an active p53. The side effects of these therapies should be minimal, since our experiments show that normal cells would arrest but not die in response to p21."
The study, published in The Journal of Biological Chemistry
, was funded by the United Kingdom's Medical Research Council (MRC), the United States' National Institute of Health (NIH), Mexico's National Council on Science and Technology (CONAYCT), and the Swedish Cancer Society.
Dr Macip believes that the findings could help scientists to identify existing drugs capable of combating specific forms of cancer.
"There are already drugs available that selectively increase p21," he explained. "Our results provide a rationale for testing them in certain types of cancers, which could be identified using the experiments we describe."