New study Natural antibiotic as a cancer therapy?

Natural product Carolacton inhibits the growth of cancer cells

Many diseases can be successfully treated with natural ingredients. In the case of cancer, too, a natural substance could significantly improve therapy in the future. The results of a recent study suggest that the natural active substance Carolacton or derived drugs could be used to inhibit cancer cell growth.

Scientists at the Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) and the Helmholtz Center for Infection Research (HZI) have investigated the effect of the natural product Carolacton in a recent study and discovered a key enzyme in folic acid metabolism as a target for the active ingredient. This opens the possibility to inhibit the growth of cancer cells with the help of Carolacton, the researchers report. Their study results were published in the journal "Nature Communications".

The natural active ingredient Carolacton inhibits the growth of cancer cells and could open new approaches to therapy. (Image: Kateryna_Kon / fotolia.com)

Natural active ingredient formed by microorganisms

Carolactone is produced as a natural active substance in soil-borne microorganisms and has antibiotic properties, the study authors report. Carolacton belongs to the class of polyketides and is isolated from the myxobacterium Sorangium cellulosum. As an antibiotic, however, the active ingredient in humans is in principle not applicable because it inhibits a key enzyme of folic acid metabolism and the latter plays a key role in most living things - including humans.

Antibacterial action of Carolactone

"Carolacton can interfere with important processes in bacteria and thus also reduce the biofilm formation of Streptococcus mutans, the main cause of dental caries," emphasizes Professor Rolf Müller, head of the department "Microbial Natural Products" and Managing Director at HIPS. At the same time, Carolacton forms a growth inhibitor of Streptococcus pneumonieae, one of the most life threatening microorganisms. In view of the effect on the folic acid metabolism, which is essential for growth, since, for example, DNA components are produced via it, Carolacton as antibiotic but barely usable. However, the target enzyme is increasingly needed by fast-growing cancer cells and these can be slowed by Carolacton in their growth, the scientists report.

Key enzyme identified for the binding of the drug

The interest of the researchers aroused above all the antibiotic activities and the antibiofilm activity of the natural active substance. The goal was a better understanding of the effect and the underlying mechanism. The model organisms Escherichia coli and Streptococcus pneumoniae allow researchers to identify the molecular target (so-called target) of the drug. Thus, Carolacton binds highly specifically to the key enzyme FolD of C1 metabolism and thereby turns it off.

Binding properties and crystal structure analyzed

According to the researchers, the key enzyme FolD is involved in the formation of folic acid in C1 metabolism (C stands for carbon). In further investigations, the crystal structure and binding properties of Carolacton on FolD could be shown in detail, reports the HZI. The C1 metabolism is one of the most important material cycles and "is highly conserved by all domains of life", emphasizes Prof. Irene Wagner-Döbler from the HZI. He provided important building blocks of growth, such as nucleic acids, amino acids and provitamins.

Use as antibiotic not possible?

Due to the key role of C1 metabolism, conserved genes for the key enzyme FolD can be found in many different species, including the mitochondria of human cells, reports Prof. Wagner-Döbler. "Due to the high degree of conservation between the bacterial FolD enzyme and the human enzyme in mitochondria, especially in the area of ​​carolactone binding sites, the natural product also inhibits the mitochondrial enzyme," continues the HZI researcher. For this reason, the use of Carolacton as an antibiotic in humans is hard to imagine.

New approach to cancer therapy

However, the researchers found that the key enzyme FolD is overproduced in many tumor cells. "Carolacton would therefore be a very good starting point for use as an inhibitor in cancer therapy," reports the HZI. "In the first experiments we were able to show inhibitory effects on different cancer cell lines tested," adds Prof. Müller. In the future, however, a further optimization of the pharmaceutical properties of the molecule must first take place. (Fp)