"This work provides proof in principle that pharmacological inhibition of calpain may be used to block cell death in situations where this is not desirable, such as in neuronal cells of Alzheimer's or Parkinson's patients, but to promote cell death in cancer cells where this is clearly a very desirable outcome," says lead researcher Peter Greer of two studies appearing in the Journal of Biological Chemistry (JBC).
Dr. Greer is a Professor of Pathology and Molecular Medicine with the Cancer Biology and Genetics division of Queen's University's Cancer Research Institute.
"All cells in our body have the ability to trigger an intrinsic programmed cell death response. In the case of nerve cells that have been temporarily cut off from their oxygen supply because of a stroke, or damaged by amyloid deposits, this might seem like a bad thing that could contribute to neurodegenerative disease," says Dr. Greer who produced the study with Yinfei Tan, Nathalie Dourdin, Chao Wu, Teresa De Veyra, and John S. Elce.
"On the other hand, when a cell's chromosomes are damaged by carcinogens or ultraviolet light in a way that could initiate cancer, this same programmed cell death response could save your life."
Supported by an operating grant from the Canadian Institute of Health Research the first study, published online and to appear in print on June 9, showed that calpain promoted programmed cell death after cells were damaged by chemicals that disrupt the endoplasmic reticulum, which is a major synthetic structure in the cell that controls the synthesis and distribution of new proteins.
In the second study, now published in JBC online, Dr. Greer and co-investigators Yinfei Tan, Chao Wu, and Teresa De Veyra, found that calpain also inhibits programmed cell death in response to other challenges, including some chemotherapeutic drugs.
This study showed that calpain contributes to the activation of AKT and JNK, two key players in the signaling pathways that control cellular responses to different death stimuli. These discoveries suggest that calpain inhibitors might improve the ability of chemotherapeutic drugs or radiation treatment to specifically kill tumour cells in cancer patients.
PLEASE NOTE: PDF copies of the studies are available upon request.
Journal
Journal of Biological Chemistry