Scientists trick cancer cells into suicide

Aug 28 2006

Scientists in the U.S. believe they have found a way to trick cancer cells into committing suicide.

The body has several defence mechanisms it can use against cells when they grow out of control and develop into tumours.

One method called apoptosis causes defective or dangerous cells to commit suicide.

This natural process of cell death involves a protein called procaspase-3 which when it is activated, changes into an enzyme called caspase-3, which triggers the cell death.

This mechanism in cancers is often faulty and cells continue to grow unchecked; many types of cancer are resistant not only to the body's own signals for cell death but also to the chemotherapy drugs that try to mimic it.

Now Paul J. Hergenrother, a professor of chemistry at the University of Illinois at Urbana-Champaign, has found a way around the natural biological process that kick starts apoptosis - a synthetic molecule that directly activates procaspase-3.

The new synthetic compound removes a molecular safety catch that activates a natural executioner in the body's cells, could lead to better treatments of cancers including those affecting the lung, skin, breast, kidney and colon.

Hergenrother says the new compound is the first in what could be a host of organic compounds with the ability to directly activate 'executioner enzymes'.

The researchers screened more than 20,000 different compounds, in their search for one with the ability to turn procaspase-3 into caspase-3.

The researchers have called the successful molecule "procaspase activating compound number one" (PAC-1).

The scientists discovered that PAC-1 killed many types of cancer cells, but it's effectiveness depended on the body's natural levels of procaspase-3.

For example, in lung cancer cells, where levels of procaspase-3 were five times higher than normal, the new molecule worked well.

Professor Hergenrother says it is now clear that many cancers have elevated concentrations of procaspase-3, while others have heightened or reduced concentrations of procaspase-3 depending on the cancer subtype.

He says 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.

This he says this may lead to personalised treatments for cancer patients in preference to more general therapies, and the amounts of drugs could be tailored to a person's condition, reducing the risk of side-effects often caused by chemotherapy.

The research is published in the current issue of Nature Chemical Biology.