The effective treatment of many forms of cancer continues to pose a major problem for medicine. Many tumours fail to respond to standard forms of chemotherapy or become resistant to the medication.
Scientists at the Helmholtz Centre for Infection Research (HZI) in Braunschweig, the Hannover Medical School (MHH) and Leibniz-Universität (LUH) in Hanover have now discovered a chemical mechanism with which a natural substance - argyrin - destroys tumours. Today, the researchers publish their findings in the renowned scientific journal "CancerCell".
The basis for this breakthrough was an observation made by the MHH scientist Prof. Nisar Malek: he had been 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."
Nisar 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: "We adapted this cell based assay system to allow automated screening of large numbers of different chemical substances."
Myxobacteria provide another potential cancer medicine
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. This drug has been approved as a cancer medicine in the USA last year. "The myxobacterial agent for our purposes is argyrin," says Ronald Frank.