New way to kill cancer cells

A Galway research team is developing a new way to attack and kill leukaemia cells, an important step in the battle against cancers…

A Galway research team is developing a new way to attack and kill leukaemia cells, an important step in the battle against cancers, writes Dick Ahlstrom.

Researchers at NUI Galway may have discovered a new way to attack cancer cells. Early results show it may be effective against a form a leukaemia, but the method could also useful for other common cancers.

"We are in the initial stages of something very exciting," explains Dr Catherine Stenson-Cox, a senior researcher in the university's National centre for Biomedical Engineering Science (NCBES).

She and PhD student Ailish O'Connell have discovered three unique molecules in the cell "that are potential candidates for the development of new drugs that could selectively kill cancer cells", Stenson-Cox explains.

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The molecules are all from a family of substances in the body known as serine proteases. These enzymes come in many forms and play a variety of roles in the body, she says. They are involved in natural cell death, known as apoptosis, but are also involved when cells break free to cause the unwanted spread of cancer.

Using a NUI Fellowship in the Sciences grant plus an award from Science Foundation Ireland administered by the Irish Research Council for Science, Engineering and Technology, Stenson-Cox began looking in fine detail at how leukaemic cells are killed when treated with chemotherapy drugs.

She was interested in serine proteases (SPs) because some years ago "it was found SPs could promote apoptosis", she explains.

Apoptosis is of intense interest to cancer and other researchers. It is a natural process of cell removal essential to life but is also a process that goes wrong in cancer, when mutated cells lose their ability to go through apoptosis and begin to grow out of control.

Researchers have learned that when apoptisis is triggered, a cascade of biochemical events is set in motion. Most of this activity involves enzymes known as caspases that begin chopping up the cell for disposal by the immune system.

Stenson-Cox has discovered a potentially novel pathway towards apoptosis however that does not appear to be dependent on caspases. "The finding here is the SP controlled cascade is independent of the caspase mediated pathway," she explains.

This new pathway is unknown and she is now trying to pick apart the complex biochemistry behind this route towards controlled cell death. She has already isolated two or three different SPs involved in the process.

Initial findings suggest this pathway somehow involves the cell's mitochondria, its energy producing machinery. It also seems that while the SPs are present in the leukaemic cells they are quiescent and have not been activated to begin apoptosis as they should have to kill off the cancerous cells.

The goal is to find ways to switch on this new cell killing system, Stenson-Cox says. "We can kill a cancer cell by activating these proteases. We do seem to have a nice specificity," she adds, meaning that the SPs will target only cancer cells and not other healthy tissues.

"The immense value to the patient of this research strategy if successful, is that we could combat cancer effectively while minimising the side effects that are usually associated with therapies," Stenson-Cox says.

She and O'Connell used very advanced technology to track the activation of the SPs, fluorescent tags provided through a collaboration with the US company, Immunochemistry Technology Inc. It showed that once set in motion the SPs were central to the apoptosis that killed off the cells.

The goal now is to better understand why the SPs remain quiescent in cancers and to look for them in actual tumours. She will also study whether activated SPs can be introduced into a tumour to kill it off.

The system has already been used to attack leukaemic cells, but she believes the method should also work in colon cancer.

Long-term studies could also include the role of apoptotic SPs in other diseases where apoptosis is not happening or is happening too readily as in Parkinson's disease.

One desirable side effect that has already come from this study is an award for O'Connell. She received the prestigious Donegan Medal for her presentation at the Royal Academy of Medicine of Ireland summer meeting hosted by the NCBES.