Scientists at the University of Illinois at Urbana-Champaign have found a way to trick cancer cells to commit suicide. The novel technique, published online in Nature Chemical Biology, potentially offers a method for providing personalized anticancer therapy.
Paul Hergenrother, Ph.D., professor of chemistry at the University of Illinois at Urbana-Champaign (UIUC) and senior author of the paper, says “We have identified a small, synthetic compound that directly activates procaspase-3 and induces apoptosis.” Most living cells contain procaspase-3, which when activated becomes caspase-3 and initiates apoptosis. In cancer cells, however, the activation process of procaspase is damaged resulting in uncontrolled growth. “By bypassing the broken apoptosis pathway, we can use the cells’ own machinery to destroy them,” adds Dr. Hergenrother.
To find the compound, called procaspase activating compound 1 (PAC-1), Dr. Hergenrother, and colleagues at UIUC, Seoul National University, and the National Center for Toxicological Research, screened more than 20,000 compounds for the ability to change procaspase-3 into caspase-3.
The researchers tested the compound’s efficacy in cell cultures and three mouse models of cancer. They also showed that PAC-1 killed cancer cells in 23 tumors obtained from a local hospital.
Cell death was correlated with the level of procaspase-3 present in the cells, with more procaspase-3 resulting in cell death at lower concentrations of PAC-1. “The potential effectiveness of 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,” explains Dr. Hergenrother, “resulting in personalized therapies”.