Scientists unlock key to cancer cell death mystery

April 5, 2012

Confocal microscopy images of HT1080p21–9 and EJp21 cells stained with MitoTracker Red CMXRos for mitochondria (red) and p21 expression (green) (credit: Masgras I., et al./Journal of Biological Chemistry)

An international team of scientists led by the University of Leicester has discovered that cells from sarcomas (a form of cancer) tend to die in response to a protein called p21, and that this effect is determined by the sensitivity of the cancer-cell mitochondria to oxidants.

The p21 protein usually forces normal and cancer cells to stop dividing but it was recently shown that in some cases it can also kill cancer cells.

According to researcher Salvador Macip, from the University of Leicester Department of Biochemistry, “If we could harness this ‘killing power’ that p21 has, we could think of designing new therapies aimed at increasing its levels in tumours. This is what motivated us to look into it.”

The research also showed that p21 can kill cells even in the absence of p53, a protein that is mostly responsible for cell death but is inactivated in most cancers.

“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,” said Macip. “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.

“There are already drugs available that selectively increase p21. Our results provide a rationale for testing them in certain types of cancers, which could be identified using the experiments we describe.”

The research team comprised scientists from the universities of Leicester and Cardiff in the UK, University of South Carolina in the U.S., and Karolinska Institutet in Sweden.

Ref.: Masgras I., et al., Reactive oxygen species and mitochondrial sensitivity to oxidative stress determine induction of cancer cell death by p21,  Journal of Biological Chemistry, Vol. 287, Issue 13, 9845-9854, 2012; [DOI:10.1074/jbc.M111.250357]