Molecule forces cancer cells to commit suicide

Karson Putt (left), Graduate Student, is currently researching new targets for the treatment of various diseases such as cancers and other neurodegenerative disorders. Putt has recently discovered that chemical named PAC1, Procaspase Activity Compound 1, Beck Diefenbach the Daily Illini

Karson Putt (left), Graduate Student, is currently researching new targets for the treatment of various diseases such as cancers and other neurodegenerative disorders. Putt has recently discovered that chemical named PAC1, Procaspase Activity Compound 1, Beck Diefenbach the Daily Illini

By Rob Warren

University researchers have discovered a way to make cancer cells commit suicide by using a new technique that exposes cancerous cells to a synthetic molecule that forces the cells to self destruct.

Karson Putt, graduate student, Paul Hergenrother, professor of chemistry, William Helferich, professor of food science and human nutrition, and other colleagues worked to discover and refine the new approach, which was published in the online edition of Nature Chemical Biology. Putt will also present the research at the American Cancer Society in San Francisco next week.

The research is not ready to be applied to humans yet, but Hergenrother said he hoped for sooner rather than later.

All cells have a system to terminate themselves, Putt said. The body does this to make sure that the cells do not continue to spread disease . However, in the case of cancers, these “executioner” functions have been in some way disabled, leading to replication and growth, he said.

The idea is best seen as a circuit, said Putt. Cells’ natural execution system gets mangled in cancers. Once one step in the wiring is broken, the current can’t get through and the cell won’t self destruct.

One of the proteins responsible for the “executioner” function is procaspase-3, the focus of the University research.

“Once procaspase-3 is activated, it’s like the point of no return,” said Putt. “The cell is doomed to die.”

Some cancers actually have elevated levels of the self-destruct protein, but the commands given by the cell are destroyed by the cancers. The treatment is suited to go after cancers with elevated levels of the protein, Putt said.

On this track, researchers looked through a library of over 20,000 molecules for a chemical to activate the execution enzyme and initiate cell death in cancer cells. The researchers found a chemical called PAC-1 which effectively activated the execution enzyme.

“We found a few candidates, two of which actually proved to be effective,” said Putt. “But PAC-1 was the best.”

By exposing the cells to the chemical, the researchers hot-wire the cells’ execution systems and skip all previous steps to force the cells into programmed cell death.

To test the effectiveness of the chemical, the researchers obtained tumors from Carle Foundation Hospital and exposed them to the compound.

“We are looking into derivatives of PAC-1 and have been very successful,” said Putt. “The derivatives are ten fold more effective than the original compound, although we are constantly trying to find new compounds.”