Many types of cancer cells have a surplus of procaspase-3. Procaspase-3 can be converted to caspase-3 which initiates the cell suicide process called apoptosis. However, cancer cells have mutations which prevent the conversion of procaspase-3 to caspase-3. Well, a team of scientists developed a drug called procaspase activating compound one (PAC-1) which converts procaspase-3 to caspase-3 and thereby initiates cell suicide.
CHAMPAIGN, Ill. -- Scientists have found a way to trick cancer cells into committing suicide. The novel technique potentially offers an effective method of providing personalized anti-cancer therapy. Most living cells contain a protein called procaspase-3, which, when activated, changes into the executioner enzyme caspase-3 and initiates programmed cell death, called apoptosis. In cancer cells, however, the signaling pathway to procaspase-3 is broken. As a result, cancer cells escape destruction and grow into tumors.
"We have identified a small, synthetic compound that directly activates procaspase-3 and induces apoptosis," said Paul J. Hergenrother, a professor of chemistry at the University of Illinois at Urbana-Champaign and corresponding author of a paper to be posted online this week ahead of regular publication by the journal Nature Chemical Biology. "By bypassing the broken pathway, we can use the cells' own machinery to destroy themselves."
To find the compound, called procaspase activating compound one (PAC-1), Hergenrother, with colleagues at the U. of I., Seoul National University, and the National Center for Toxicological Research, screened more than 20,000 structurally diverse compounds for the ability to change procaspase-3 into caspase-3.
The treatment works because procaspase-3 is often much more abundant in cancer cells than in healthy cells, says Paul Hergenrother at University of Illinois in Urbana, US, who led the study: In tissue from 23 colon cancer patients we found that, on average, levels of procaspase-3 are eightfold higher than in healthy cells sometimes as much as 20-fold higher.
Healthy cells, such as white blood cells, were found to be significantly less affected by the addition of PAC-1 because they had much lower levels of procaspase-3, so cell-suicide could not be triggered.
When the scientists tested PAC-1 on cancerous and non-cancerous tissue from the same person, the tumour cells were 2,000-fold more sensitive to PAC-1.
"It is now clear that many cancers have elevated concentrations of procaspase-3," wrote Prof Hergenrother in the Nature paper. "Others have heightened or reduced concentrations of procaspase-3 depending on the cancer subtype." He added that a systematic analysis of procaspase-3 concentrations in a variety of cancer types was needed to determine which cancers would be most amenable to treatment with a molecule such as PAC-1.
The continued discovery of differences between cancerous and normal cells will provide more targets for anti-cancer drug development. The continued advance in general understanding of cell metabolism and gene regulation will lead to the discovery of many more enzymes and intra-cellular messengers which will become targets for anti-cancer drug development.
I am very optimistic that most of us will live long enough to witness the total defeat of cancer.
|Share |||Randall Parker, 2006 August 27 10:31 PM Biotech Cancer|