Synthetic molecule causes cancer cells to self-destruct

August 27, 2006

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 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.

Source: University of Illinois at Urbana-Champaign

Related Stories

Recommended for you

Researchers discover new 'GPS' neuron

May 29, 2017

An international research team led by the University of Amsterdam researchers Jeroen Bos, Martin Vinck and Cyriel Pennartz has identified a new type of neuron which might play a vital role in humans' ability to navigate their ...

Neurons can learn temporal patterns

May 29, 2017

Individual neurons can learn not only single responses to a particular signal, but also a series of reactions at precisely timed intervals. This is what emerges from a study at Lund University in Sweden.

How self-regulation can help young people overcome setbacks

May 29, 2017

Failing an exam at school, getting rejected for a job or being screamed at by your teacher or superior are only a few examples of situations that may cause despair, disappointment or a sense of failure. Unfortunately, such ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.