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Molecule triggers cancer cell suicide
Source: (cancerfacts.com)
Tuesday, August 29, 2006
CHAMPAIGN, Ill. – Aug. 29, 2006 – Scientists have found a way to trick cancer cells into committing suicide using a newly discovered molecule that activates a cell protein that is often disabled when cells are converted to cancer.
Led by Dr. Paul Hergenrother, a professor of chemistry at the University of Illinois at Urbana-Champaign, the research team found the chemical molecule after an exhaustive search for a way to directly activate a protein called procaspase-3, which is typically turned off when cells turn into cancer.
"We have identified a small, synthetic compound that directly activates procaspase-3 and induces apoptosis," Hergenrother said in a prepared statement. "By bypassing the broken pathway, we can use the cells' own machinery to destroy themselves." The research appears this week online, ahead of publication in the September issue of the journal Nature Chemical Biology.
The novel technique potentially offers an effective method of providing personalized anti-cancer therapy. Most living cells contain a protein called procaspase-3, which, when activated, changes into the executioner enzyme caspase-3 and initiates programmed cell death, or apoptosis. In cancer cells, however, the signaling pathway to procaspase-3 is broken. As a result, cancer cells escape destruction and grow into tumors.
To find the compound, called procaspase activating compound one (PAC-1), Hergenrother, and colleagues at the University of Illinois, Seoul National University, and the National Center for Toxicological Research, screened more than 20,000 structurally diverse compounds for the ability to change procaspase-3 into caspase-3, which is the active form of the protein that triggers programmed cell death.
The researchers tested the compound's effectiveness in cell cultures and in three mouse models of cancer. The testing was performed in collaboration with Dr. William Helferich, a professor of food science and human nutrition at the University of Illinois, and Dr. Myung-Haing Cho at Seoul National University. The researchers also showed that PAC-1 killed human cancer cells in 23 tumors obtained from a local hospital.
Cell death effectiveness was linked to the level of procaspase-3 present in the cells, with more procaspase-3 in the cell resulting in cell death at lower concentrations of PAC-1.
"This is the first in what could be a host of organic compounds with the ability to directly activate executioner enzymes," said Hergenrother, who is also an affiliate of the Institute for Genomic Biology at the U. of I. "The potential effectiveness of compounds such as 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."
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