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Synthetic molecule causes cancer
cells to self-destruct
James E. Kloeppel, Physical Sciences Editor
photo to enlarge
by L. Brian Stauffer
white board is diagram of the synthetic
molecule that signals cell death in cancer
cells, identified by Illinois researchers:
seated from left, Bill Helferich, professor of
nutritional sciences; Paul Hergenrother, professor
of chemistry, and Karson Putt, graduate research
assistant in chemistry; and standing from left,
Joe Sandhorst, graduate research assistant
in chemistry, and Martin Hoagland, postdoctoral
student in veterinary biosciences.
CHAMPAIGN, Ill. —
Scientists have found a way to trick cancer cells into committing suicide.
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, 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
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
“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
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.
The work was funded by the National Science Foundation, the National
Institutes of Health, and the University of Illinois.
Editor’s note: To reach Paul Hergenrother,
call 217-333-0363; e-mail: email@example.com.