Washington, July 9 : Scientists at the Helmholtz Centre for Infection Research (HZI) in Braunschweig, the Hannover Medical School (MHH) and Leibniz-Universitat in Hanover have discovered a chemical mechanism with which a natural substance - argyrin - destroys cancerous tumours.
The study has been published in the renowned scientific journal "CancerCell".
The basis for this breakthrough was an observation made by the MHH scientist Prof. Nisar Malek.
Malek was studying the role of a certain protein - a so-called cyclin-kinase inhibitor - in the development of cancer. In the process, Malek noted that mice in which the breakdown of the kinase inhibitor was suppressed by genetic change have a significantly lower risk of suffering from intestinal cancer.
"I needed a substance that would prevent the breakdown of the protein that I was investigating in the cancer cells," says Nisar Malek.
"This molecule, in all likelihood, would make a good anti-cancer agent," Malek added.
Then, Malek approached Dr. Ronald Frank, a chemist at HZI, with his considerations.
Ronald Frank has established extensive collections of chemical substances at the HZI that can be tested for their biological activity in a fast, automated procedure. The two agreed to develop a special cell line in which the quantity of the cyclin kinase inhibitor can be measured using simple optical methods.
Ronald Frank said: "We adapted this cell based assay system to allow automated screening of large numbers of different chemical substances."
"Myxobacteria provide another potential cancer medicine," he added.;
Malek and Frank found what they were looking for in a collection of natural substances, which had originally been isolated from microorganisms, which live in soil - the so-called Myxobacteria.
Myxobacteria have proven to be a treasure trove of potential medicines, also being used in the production of epothilone, an active agent identified at the HZI.
"The myxobacterial agent for our purposes is argyrin," said Frank.
With this knowledge, Ronald Frank and Nisar Malek joined up with the chemist Prof. Markus Kalesse of the LUH to launch an extensive research programme to discover how argyrin can be produced chemically and how it functions. In the process they stumbled upon a completely new mechanism.
"Argyrin blocks the molecular machinery of the cell which breakdowns proteins that are no longer required, and thereby naturally also prevents the breakdown of the kinase inhibitor in question, the lack of which triggers cancer," Malek said.