Scientists pit element in cancer, diabetes fight

by Hilary Thomson
Staff writer

It can strengthen steel, shrink tumors, sink sugar levels and for almost 14 years it's been the focus of research for Chemistry Prof. Chris Orvig and Prof. John McNeill of the Faculty of Pharmaceutical Sciences.

What is this versatile substance? It's called vanadium -- a naturally occurring element traditionally used to make steel alloys.

The two researchers recently received Natural Sciences and Engineering Research Council of Canada (NSERC) grants of more than $700,000 to continue their investigations of vanadium for the next three years.

"The grants will help us develop vanadium compounds to the point where we can test their effectiveness on people, both diabetics and cancer patients," says McNeill, a former dean of the Faculty of Pharmaceutical Sciences.

Since the early '80s, he has been studying how vanadium compounds can help combat diabetes.

Diabetes is characterized by excessive blood glucose levels. It occurs when there is a drop in the amount of insulin produced in the body or a decrease in cells' response to insulin.

Defects in the cells of fat tissues, skeletal muscle and the liver interfere with the pathway of chemical signals that tell the body how to process glucose.

McNeill found that vanadium compounds could correct the defective signalling pathways and increase the cells' response to insulin, which would aid normal processing of sugar in patients with diabetes.

In laboratory testing, he also found that vanadium could reduce high blood pressure and extreme overweight, both effects of the disorder.

There was just one problem - vanadium was not easily absorbed into tissue. That's when he called Orvig, who is director of the Medicinal Inorganic Chemistry Group, an interdisciplinary UBC research team.

Orvig was able to increase the compound's absorption rate by chemically binding vanadium to maltol, a food additive, and to other organic chemicals. The body can process the resulting compounds more efficiently because of their organic components.

They are also more potent and less toxic because less of the chemical is required to produce the same effect.

The anti-diabetic compounds that McNeill and Orvig invented were licensed to Kinetek, a UBC spin-off biotech company specializing in therapeutics based on modifying signalling pathways. The two researchers will continue to work with Kinetek in developing the compounds, supported in part by the recent NSERC grant.

Kinetek expects to apply for clinical trials testing of vanadium compound therapies for diabetes before the end of the year.

The compounds synthesized by Orvig have also been the focus of collaborative research with Angiotech, a pharmaceutical company that develops treatments for cancer and chronic inflammatory diseases.

Researchers found that vanadium compounds could block the pathway that leads to the uncontrolled cell growth and division seen in cancer.

"The beauty of the vanadium compounds is that they act on different biological targets than have been used before," says Orvig.

DNA and RNA are typical targets of more traditional chemotherapies. The chemicals break up DNA and RNA molecules, making cells non-functional and unable to grow. Drugs containing vanadium, however, zero in on the signalling pathways to change the communication within cells, especially tumor cells.

Pre-clinical studies showed the vanadium-based agents to be particularly effective in reducing some types of lung tumors. An important feature is their effectiveness against tumor cells resistant to other anti-cancer drugs.

In addition, research suggests that vanadium compounds do not cause suppression of the immune system, a side effect of conventional chemotherapies.

Orvig, together with Angiotech, will continue to develop vanadium compounds.