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 Unidentified spectra detector
28.06.2016 | European Molecular Biology Laboratory - European Bioinformatics Institute

nachricht Freiburg Biologists Explain Function of Pentagone
28.06.2016 | Albert-Ludwigs-Universität Freiburg im Breisgau

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Flexible OLED applications arrive

R2D2, a joint project to analyze and development high-TRL processes and technologies for manufacture of flexible organic light-emitting diodes (OLEDs) funded by the German Federal Ministry of Education and Research (BMBF) has been successfully completed.

In contrast to point light sources like LEDs made of inorganic semiconductor crystals, organic light-emitting diodes (OLEDs) are light-emitting surfaces. Their...

Im Focus: Unexpected flexibility found in odorant molecules

High resolution rotational spectroscopy reveals an unprecedented number of conformations of an odorant molecule – a new world record!

In a recent publication in the journal Physical Chemistry Chemical Physics, researchers from the Max Planck Institute for the Structure and Dynamics of Matter...

Im Focus: 3-D printing produces cartilage from strands of bioink

Strands of cow cartilage substitute for ink in a 3D bioprinting process that may one day create cartilage patches for worn out joints, according to a team of engineers. "Our goal is to create tissue that can be used to replace large amounts of worn out tissue or design patches," said Ibrahim T. Ozbolat, associate professor of engineering science and mechanics. "Those who have osteoarthritis in their joints suffer a lot. We need a new alternative treatment for this."

Cartilage is a good tissue to target for scale-up bioprinting because it is made up of only one cell type and has no blood vessels within the tissue. It is...

Im Focus: First experimental quantum simulation of particle physics phenomena

Physicists in Innsbruck have realized the first quantum simulation of lattice gauge theories, building a bridge between high-energy theory and atomic physics. In the journal Nature, Rainer Blatt‘s and Peter Zoller’s research teams describe how they simulated the creation of elementary particle pairs out of the vacuum by using a quantum computer.

Elementary particles are the fundamental buildings blocks of matter, and their properties are described by the Standard Model of particle physics. The...

Im Focus: Is There Life On Mars?

Survivalist back from Space - 18 months on the outer skin of the ISS

A year and a half on the outer wall of the International Space Station ISS in altitude of 400 kilometers is a real challenge. Whether a primordial bacterium...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Conference ‘GEO BON’ Wants to Close Knowledge Gaps in Global Biodiversity

28.06.2016 | Event News

ERES 2016: The largest conference in the European real estate industry

09.06.2016 | Event News

Networking 4.0: International Laser Technology Congress AKL’16 Shows New Ways of Cooperations

24.05.2016 | Event News

 
Latest News

Rotating ring of complex organic molecules discovered around newborn star

28.06.2016 | Physics and Astronomy

Unidentified spectra detector

28.06.2016 | Life Sciences

Clandestine black hole may represent new population

28.06.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>