Breast milk for the prevention of cancer?
Remodeled protein molecule recognizes and kills cancer cellsRead out
Remedies from breast milk? Scientists have rebuilt a specific ingredient of human breast milk to fight cancer cells. The protein molecule is part of the innate immune system and naturally occurs against altered body cells. Thanks to the researchers' optimization, the peptide now recognizes forms of cancer that are difficult to treat - and is particularly effective at warding off diseased cells. However, the promising results from animal experiments must be confirmed by further studies.
Many cancers today are curable if the tumors are detected in time and there are effective chemotherapeutic agents against them. However, despite advances in medicine, some cancers are still considered difficult to treat - for example skin cancer, tumors in the brain or cancer that has already spread and metastasized.
For physicians, the challenge with these treacherous diseases is first of all to detect the cancer cells in the body and, secondly, to fight them successfully. Scientists led by Dagmar Zweytick from the University of Graz have now developed a method that could possibly do better in the future, even in poorly treatable forms of cancer.
Drug search in breast milk
In search of an effective weapon against stubborn cancer cells, the researchers dedicated a typical identifying feature of the culprits: Unlike healthy cells, the membrane envelope of each cancer cell on the outside carries negatively charged molecules in the form of the lipid phosphatidylserine. This lipid can detect tumors and even metastases - it can therefore serve as a cancer marker.
But how can this job be reliably identified? Zweyticks and her colleagues tested as a possible arrowhead, which independently targets the lipid and thus all cancer cells, a substance from human breast milk: the peptide lactoferricin. The small protein molecule is part of the innate immune system that supplies the newborn with breast milk. display
Lactoferricin acts as the first defense reaction against negatively charged foreign body cells such as bacteria and fungi, but also against altered endogenous cells. The suspicion was therefore obvious that it could also detect and fight cancer cells.Skin cancer cells before (left), after 4-hour and 8-hour (right) treatment: The increasing uptake of the red dye indicates severe membrane damage and final cell death. Sabrina Riedl / Dagmar Zweytick / Uni Graz
Peptide arrow meets cancer cells
For less than four years, the scientists worked to optimize the peptide for use as an antitumour agent. In doing so, they deliberately rearranged a certain part of the molecule in such a way that it recognizes, among other things, melanomas and so-called glioblastomas in the brain. The positively charged peptide arrows find the negatively charged, phosphatidylserine-studded surface of the cancer cells, dock and release within a few hours from cell death.
The way to the finished drug was long, as the researchers report. So they first simulated which variants of the molecule are as active as possible. They then synthesized fifteen variants to test on cell cultures. "The biggest challenge in the design process was finding the right balance of toxicity and specificity. If the peptide fragments become too active, they also attack healthy body cells. In control trials, we have repeatedly reassured ourselves that only cancer cells are found and normal cells spared, "say the team.
Tumor shrinkage in mice
With the two most promising drug candidates, Zweyticks and her colleagues finally performed experiments on mice. They compared how rodents developed with human cancers with and without treatment with the peptide. The result: In the peptide-treated mice, there was a strong reduction of tumors by an average of 85 percent in melanoma and up to 50 percent in glioblastoma.
Both drug variants were about ten times more potent than the molecule originally contained in breast milk, as the researchers report. Experiments with healthy Kontrollm usen also demonstrated that the drugs cause no harmful side effects.
The scientists have already applied for a patent for their peptides in the European Union and in the USA. Together with a pharmaceutical company, they are now working on testing the drug in further studies. If the antitumor agent from breast milk should eventually be approved for therapy in humans, it would preferably be injected via the vein in order to achieve metastases.
It is therefore also necessary to check how stable the peptide arrow is in the blood system, whether a penetration of the blood-brain barrier is possible and how the arrowhead can be further strengthened, concludes the team,
(The Science Fund FWF, 11.04.2017 - DAL)