CHAMPAIGN, Illinois: Scientists have developed a new synthetic compound that can trick cancer cells to commit self-destruction. The compound can initiate programmed cell death, or apoptosis, which does not happen in cancer cells because the signaling path to a protein called procaspase-3 is broken in such cells, leading to the cancer cells escaping destruction and growing into tumors.
Paul Hergenrother, a professor of chemistry at the University of Illinois at Urbana-Champaign and a corresponding author of a paper to be published in the journal Nature Chemical Biology, says his team has invented a synthetic compound that directly activates procaspase-3 and induces apoptosis.
This will lead to bypassing the broken pathway in cancer cells and the cells' own machinery will be activated to destroy themselves. He believes the compound could lead to better cancer treatments, including cancers of the lung, skin, breast, kidney and colon.
Cell suicide, or apoptosis, is one of the several methods used by the body to prevent cells from growing out of control and developing into tumors. This natural process involves procaspase-3, which when activated, changes into an enzyme called caspase-3, which in turn causes the cell death. In cancers, this mechanism is rendered faulty and cells do not die but grow unchecked. Several types of cancers have been found to be not only resistant to apoptosis but even to chemotherapy drugs that attempt to mimic the process.
The new compound is found to directly activate procaspase-3. Prof Hergenrother says this is the first in what could be a host of organic compounds with the ability to directly activate executioner enzymes.
The scientists involved in the study -- from the University of Illinois at Urbana-Champaign, Seoul National University and the National Center for Toxicological Research -- screened more than 20,000 different compounds, looking for the one with the ability to turn procaspase-3 into caspase-3. They could successfully develop what they named procaspase activating compound number one (PAC-1).
They then tested the compound in cell cultures and three mouse models of cancer and found that it activated cell suicide. They also tested it in 23 tumors obtained from a local hospital and found that it killed these cells.
The scientists say that PAC-1 killed many types of cancer cells, but how well it worked depended on the body's natural levels of procaspase-3. The higher the levels, the better is the result, they said.
Hergenrother writes in the article that a systematic analysis of procaspase-3 concentrations in a variety of cancer types is needed to determine which cancers would be most amenable to treatment with PAC-1.
He adds that since testing cancers for procaspase-3 could lead to personalized treatments for cancer patients, the potential effectiveness of a compound such as PAC-1 could be assessed with a high degree of accuracy and people with cancer could be pre-selected for treatment with a procaspase-3 activator based on the concentration of procaspase-3 in their tumor cells.
