Featured Research
from universities, journals, and other organizations
New enzyme targets for selective cancer therapies
Date:
August 22, 2014
Source:
University of Alberta
Summary:
Compounds that target
brain cancer have been recently developed by researchers. The 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.
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.
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.
"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, we can affect those interactions." -- Christopher Cairo, U of A
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."
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.
"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, we can affect those interactions." -- Christopher Cairo, U of A
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."
Story Source:
The above story is based on materials provided by University of Alberta. The original article was written by Bryan Alary. Note: Materials may be edited for content and length.
The above story is based on materials provided by University of Alberta. The original article was written by Bryan Alary. Note: Materials may be edited for content and length.
Journal Reference:
- I Silvestri, F Testa, R Zappasodi, C W Cairo, Y Zhang, B Lupo, R Galli, M Di Nicola, B Venerando, C Tringali. Sialidase NEU4 is involved in glioblastoma stem cell survival. Cell Death and Disease, 2014; 5 (8): e1381 DOI: 10.1038/cddis.2014.349
Cite This Page:
Share This
More Health & Medicine News
Sunday, August 24, 2014
Featured Research
from universities, journals, and other organizations
Study of Self-Awareness in MS Has Implications for Rehabilitation
Aug. 23, 2014 — Persons with MS may be
able to improve their self-awareness through task-oriented cognitive
rehabilitation, a study shows. Self-awareness is one's ability to
recognize cognitive problems caused by ... full story
- MS Study Has Implications for Rehab
- Coping Skills Training For Rheumatoid Arthritis
- New Enzyme Targets for Selective Cancer Therapies
- Women With Chronic Health Issues: Less Screening
- Online Screening for Rare Lung Cancer Mutation
- Many Lack Knowledge About Ebola, Its Transmission
- Risk of Premature Menopause Post-Cancer Treatment
- Pomegranate Drug to Aid Alzheimer's, Parkinson's?
- Epigenetic Changes in Kids With Crohn's Disease
- Gamified Health Apps: Putting Odds in Your Favor?
newer top stories | older top stories
Featured Videos
from AP, Reuters, AFP, and other news services
No comments:
Post a Comment
Please leave a comment-- or suggestions, particularly of topics and places you'd like to see covered