Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New enzyme targets for selective cancer therapies

25.08.2014

UAlberta team designs compound that targets brain cancer.

Thanks to important discoveries in basic and clinical research and technological advances, the fight against cancer has mobilized into a complex offensive spanning multiple fronts.


Chemistry professor Christopher Cairo and his team synthesized a compound that inhibits an enzyme linked to brain cancer—a finding that could lead to new drugs that are better able to target cancer. (Photo: Richard Siemens)

Work happening in a University of Alberta chemistry lab could help find new and more selective therapies for cancer. Researchers have developed a compound that targets a specific enzyme overexpressed in certain cancers—and they have tested its activity in cells from brain tumours. Chemistry professor Christopher Cairo and his team synthesized a first-of-its-kind inhibitor that prevents the activity of an enzyme called neuraminidase.

Although flu viruses use enzymes with the same mechanism as part of the process of infection, human cells use their own forms of the enzyme in many biological processes. Cairo's group collaborated with a group in Milan, Italy, that has shown that neuraminidases are found in excess amounts in glioblastoma cells, a form of brain cancer.

In a new study, a team from the University of Milan tested Cairo’s enzyme inhibitor and found that it turned glioblastoma cancer stem cells—found within a tumour and believed to drive cancer growth—into normal cells. The compound also caused the cells to stop growing, suggesting that this mechanism could be important for therapeutics. Results of their efforts were published Aug. 22 in the Nature journal Cell Death & Disease.

Cairo said these findings establish that an inhibitor of this enzyme could work therapeutically and should open the door for future research. “This is the first proof-of-concept showing a selective neuraminidase inhibitor can have a real effect in human cancer cells,” he said. “It isn’t a drug yet, but it establishes a new target that we think can be used for creating new, more selective drugs.”

Long road from proof of concept to drug Proving the compound can successfully inhibit the neuraminidase enzyme in cancer cells is just the first step in determining its potential as a therapy. In its current form, the compound could not be used as a drug, Cairo explained, largely because it wasn't designed to breach the blood-brain barrier making it difficult to reach the target cells. The team in Milan had to use the compound in very high concentrations, he added.

The research advances our understanding of how important carbohydrates are to the function of cells. Although most of us think of glucose (blood sugar) as the only important sugar in biology, there is an entire area of research known as glycobiology that seeks to understand the function of complex carbohydrate structures in cells. Carbohydrate structures cover the surface of cells, and affect how cells interact with each other and with pathogens.

Scientists have known for decades that the carbohydrates found on cancer cells are very different from those on normal cells.

For example, many cancers have different amounts of specific residues like sialic acid, or may have different arrangements of the same residues. “The carbohydrates on the cell surface determine how it interacts with other cells, which makes them important in cancer and other diseases. So, if we can design compounds that change these structures in a defined way, we can affect those interactions,” Cairo explained.

“Finding new enzyme targets is essential to that process, and our work shows that we can selectively target this neuraminidase enzyme.” Although there has been a lot of work on targeting viral neuraminidase enzymes, Cairo’s team has found inhibitors of the human enzymes. "The challenge in human cells is that there are four different isoenzymes.

While we might want to target one for its role in cancer, hitting the wrong one could have harmful side-effects," he said. The U of A team reached out to their colleagues in Milan who were studying the role of a specific neuraminidase isoenzyme in cancer cells isolated from patients. Cairo approached them about testing a compound his team identified last year, which was selective for the same isoenzyme.

“I expected it would do something, but I didn’t know it would be that striking. It came out beautifully,” Cairo said. The U of A team is already working on improving the compound, and developing and testing new and existing inhibitors using a panel of in vitro assays they developed.

“We’ve been working on these enzymes for about five years. Validation of our strategy­­­—design of a selective neuraminidase inhibitor and application in a cell that overexpresses that enzyme—is an achievement for us.” The U of A’s team was funded by the Alberta Glycomics Centre, the Cancer Research Society and the Natural Sciences and Engineering Research Council of Canada.

Bryan Alary | Eurek Alert!
Further information:
http://uofa.ualberta.ca/news-and-events/newsarticles/2014/august/new-enzyme-targets-for-selective-cancer-therapies

Further reports about: Cell Nature activity compound enzyme function mechanism specific structures sugar therapy

More articles from Life Sciences:

nachricht If Machines Could Smell ...
19.07.2019 | Fraunhofer-Institut für Produktionstechnik und Automatisierung IPA

nachricht Algae-killing viruses spur nutrient recycling in oceans
18.07.2019 | Rutgers University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Better thermal conductivity by adjusting the arrangement of atoms

Adjusting the thermal conductivity of materials is one of the challenges nanoscience is currently facing. Together with colleagues from the Netherlands and Spain, researchers from the University of Basel have shown that the atomic vibrations that determine heat generation in nanowires can be controlled through the arrangement of atoms alone. The scientists will publish the results shortly in the journal Nano Letters.

In the electronics and computer industry, components are becoming ever smaller and more powerful. However, there are problems with the heat generation. It is...

Im Focus: First-ever visualizations of electrical gating effects on electronic structure

Scientists have visualised the electronic structure in a microelectronic device for the first time, opening up opportunities for finely-tuned high performance electronic devices.

Physicists from the University of Warwick and the University of Washington have developed a technique to measure the energy and momentum of electrons in...

Im Focus: Megakaryocytes act as „bouncers“ restraining cell migration in the bone marrow

Scientists at the University Würzburg and University Hospital of Würzburg found that megakaryocytes act as “bouncers” and thus modulate bone marrow niche properties and cell migration dynamics. The study was published in July in the Journal “Haematologica”.

Hematopoiesis is the process of forming blood cells, which occurs predominantly in the bone marrow. The bone marrow produces all types of blood cells: red...

Im Focus: Artificial neural network resolves puzzles from condensed matter physics: Which is the perfect quantum theory?

For some phenomena in quantum many-body physics several competing theories exist. But which of them describes a quantum phenomenon best? A team of researchers from the Technical University of Munich (TUM) and Harvard University in the United States has now successfully deployed artificial neural networks for image analysis of quantum systems.

Is that a dog or a cat? Such a classification is a prime example of machine learning: artificial neural networks can be trained to analyze images by looking...

Im Focus: Extremely hard yet metallically conductive: Bayreuth researchers develop novel material with high-tech prospects

An international research group led by scientists from the University of Bayreuth has produced a previously unknown material: Rhenium nitride pernitride. Thanks to combining properties that were previously considered incompatible, it looks set to become highly attractive for technological applications. Indeed, it is a super-hard metallic conductor that can withstand extremely high pressures like a diamond. A process now developed in Bayreuth opens up the possibility of producing rhenium nitride pernitride and other technologically interesting materials in sufficiently large quantity for their properties characterisation. The new findings are presented in "Nature Communications".

The possibility of finding a compound that was metallically conductive, super-hard, and ultra-incompressible was long considered unlikely in science. It was...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on UV LED Technologies & Applications – ICULTA 2020 | Call for Abstracts

24.06.2019 | Event News

SEMANTiCS 2019 brings together industry leaders and data scientists in Karlsruhe

29.04.2019 | Event News

Revered mathematicians and computer scientists converge with 200 young researchers in Heidelberg!

17.04.2019 | Event News

 
Latest News

Heat flow through single molecules detected

19.07.2019 | Physics and Astronomy

Heat transport through single molecules

19.07.2019 | Physics and Astronomy

Welcome Committee for Comets

19.07.2019 | Earth Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>