August 28, 2006
New Compound Causes Cancer Cell SuicideTopics: Medical Science News
One of the hallmarks of cancer cells is their resistance to the body's cell suicide signals, which allow them to survive and develop into tumours. Athough all cells contain a protein called procaspase-3, which enables the body to turn into caspase-3 (a key mediator of apoptosis of mammalian cells), this transformation does not happen in cancer cells, even though certain types of cancer cells contain very high levels of procaspase-3.
Now we are hearing that a University of Illinois team has created a synthetic molecule which induced apoptosis in cancer cells, and they claim that it offers "exciting possibilities" for new ways of treating the disease:
In preparation for apoptosis, a chain of chemical events takes place in the cell. Near the end, the chemical procaspase-3 is activated. This chemical then transforms into caspase-3--an executioner enzyme that terminates the cell. Chemist Paul Hergenrother of the University of Illinois and an international team of colleagues realized that a compound that activated procaspase-3 might be effective in killing cancer, because many tumors show elevated levels of procaspase despite their inability to complete apoptosis. After screening 20,500 related molecules for this activation ability, the researchers narrowed it down to five likely candidates. Of these, only one showed an increasingly strong effect with increased doses: newly named procaspase activating compound, or PAC-1.The researcher suggests that the potential effectiveness of compounds such as PAC-1 could be predicted in advance and patients could be selected for treatment based on the amount of procaspase-3 found in their tumor cells.
... We have identified a small, synthetic compound that directly activates procaspase-3 and induces apoptosis," Hergenrother says. "By bypassing the broken pathway, we can use the cells' own machinery to destroy them."
The researchers tested the efficacy of PAC-1 on colon cancer cells ... from 23 patients. The tumors had elevated levels of procaspase-3 averaging roughly eight times as much as normal colon cells and proved more sensitive to the compound. In one case, the cancerous cells were 2,000 times more sensitive to PAC-1's enforced apoptosis than were surrounding regular cells due to their increased expression of the enzyme. Further tests in mice proved effective in treating grafted human kidney- and lung-cancer cells, and those results also indicated that PAC-1's strength correlated with procaspase-3 levels in the various cancer cells.
Posted by Richard at August 28, 2006 6:00 AM
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