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Senior Citizen Health & Medicine
PAC-1 Compound Causes Cancer Cells to Self-Destruct
May lead to personalized anti-cancer therapy,
scientists say
 August 28, 206- A compound called PAC-1 can trick
cancer cells into committing suicide, say researcher, who predict this
novel technique potentially could lead to an effective method of
providing personalized anti-cancer therapy.
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Most living cells contain a protein called
procaspase-3, which, when activated, changes into the executioner enzyme
caspase-3 and initiates programmed cell death, called apoptosis. In
cancer cells, however, the signaling pathway to procaspase-3 is broken.
As a result, cancer cells escape destruction and grow into tumors.
"We have identified a small, synthetic compound
that directly activates procaspase-3 and induces apoptosis," said Paul
J. Hergenrother, a professor of chemistry at the University of Illinois
at Urbana-Champaign and corresponding author of a paper to be posted
online this week ahead of regular publication by the journal Nature
Chemical Biology. "By bypassing the broken pathway, we can use the
cells' own machinery to destroy themselves."
To find the compound, called procaspase activating
compound one (PAC-1), Hergenrother, with colleagues at the U. of I.,
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.
The researchers tested the compound's efficacy in
cell cultures and in three mouse models of cancer. The testing was
performed in collaboration with William Helferich, a professor of food
science and human nutrition at the U. of I., and Myung-Haing Cho at
Seoul National University. The researchers 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.
"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."
Such personalized medicine strategies are
preferential to therapies that rely on general cytotoxins, the
researchers say, and could be the future of anti-cancer therapy.
About study:
The work was funded by the National Science
Foundation, the National Institutes of Health, and the University of
Illinois.
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