College of LAS « Illinois

Chemistry

The Executioner Destroys Cancer Cells

Synthetic compound can trigger cells to self-destruct.

cells

It can happen any time of the day. One of Paul Hergenrother's graduate students gets a call on his cell phone and drops everything to rush to Carle Hospital, just a short drive from the University of Illinois chemistry department.

This graduate student is racing over to pick up a colon cancer tumor, freshly removed from a patient.

Hergenrother, a chemistry professor in LAS, uses these tumors to test the effectiveness of a bold new treatment for cancer. His team has discovered a small, synthetic compound that can turn the procaspase–3 protein into an "executioner enzyme." The executioner enzyme, in turn, causes cancer cells to self–destruct.

In mouse studies and in colon cancer samples, Hergenrother has found that if cancer cells contain elevated levels of procaspase–3, the researchers' synthetic compound can trigger the cells' self–destruct mechanism. This is good news in the battle against colon, breast, and lung cancer because these types of cancer cells typically contain high levels of that protein. For instance, the colon tumors used in Hergenrother's research had up to 20 times the level of procaspase–3 found in normal, healthy cells.

In a healthy cell, normal levels of procaspase–3 are enough to cause a cell to self–destruct whenever it has been damaged by sunlight, chemicals, or other causes. But in cancer cells, the signaling pathway to procaspase–3 is broken, so the self–destruct mechanism does not activate.

The researchers' new compound, known as "procaspase activating compound one" (PAC–1) overcomes this problem.

According to Hergenrother, they are just now beginning toxicity tests, which will check to make sure the compound has no harmful side effects on healthy cells. But because the compound targets only cells with elevated levels of procaspase–3, healthy cells should be spared.

Hergenrother says these types of "personalized strategies" could be the future of anti–cancer treatments. By "personalized," he means treatments that target a specific type of cancer, which may be more effective than giving patients general cytotoxin treatments that kill all rapidly dividing cells.

In this case, PAC–1 would be most effective against colon, breast, and lung cancer. But he envisions other compounds that could target different forms of cancer.

In Hergenrother's lab, his team has more than 20,000 different compounds that they can screen for various medicinal purposes. In early 2007, his screening system will be even more efficient with the opening of the High–Throughput Screening Facility in the college's legendary Noyes Laboratory—a national chemistry landmark.

The High–Throughput Screening Facility will allow Hergenrother and other researchers to screen as many as 100,000 compounds using an automated system in which robotic arms replace some of the more tedious duties now performed by graduate students.

"Everyone in the University can have access to the compounds in this facility," Hergenrother says. "Whatever biological pathway problem they're interested in, they can use this tool."

Fall/Winter 2006–07