The chemical that gives mown hay its sweet smell also has potential as an anti-cancer agent, according to researchers at IT Tallaght. Dick Ahlstrom looks at their findings
An Irish student is heading for a new research post at Harvard Medical School, thanks to his involvement in a cancer research group at the Institute of Technology Tallaght.
The group is looking at drugs that can disrupt activities inside tumour cells as a way to kill them off while leaving healthy cells intact.
The research is all about signalling inside the cell, according to Dr Denise Egan of Tallaght's Department of Applied Science. The goal is to understand the crucial intracellular signalling, then interrupt this with substances able to break the signalling, bringing about controlled cell death.
A student working under Dr Egan, Greg Finn, recently completed his PhD on cellular signalling. He did his initial National Cert in Science at Tallaght then went on to finish his National Diploma in science, a BSc Hons in bioanalytical science, and finally his PhD. "He is the first one through from cert to PhD," says Dr Egan.
Finn sent out resumes and was quickly picked up by Harvard. He has been offered a post at the Beth Israel Medical Centre linked to Harvard Medical School, Boston.
Tallaght has now joined with Dublin Institute of Technology and NUI Maynooth to form the "Pharma R&D Team". This multidisciplinary group includes synthetic organic and inorganic chemists, analysts, microbiologists, pharmacologists, toxicologists and molecular biologists.
The object is to develop compounds that are better than existing commercial products. The team is concentrating in two areas, anti-cancer chemotherapeutic drugs and antimicrobial agents. "This is a direct lead-on from what Greg was doing with us," says Egan.
They are looking in particular at three compounds: coumarins, phenanthrolines and benzimidazoles.
The first is a natural substance that gives cut hay its sweet smell. An Irish researcher discovered in the 1950s that it had anticancer properties. The other two are synthetic compounds and both have good antimicrobial activity.
"We are making new derivatives of these, changing the structures of the compounds ever so slightly to see if we can increase their antimicrobial and anticancer properties." explains Egan. Maynooth will assess the antimicrobial properties and Tallaght will look at the anticancer potential.
Egan's main research partner at Tallaght is Dr Bernie Creaven who will handle synthesis. For testing purposes Tallaght is using an in vitro system based on twin lines of kidney cells.
"We have what are called matched cell lines," explains Egan. "One is non-cancerous and the other is a cancer cell line."
They are almost identical, with the non-cancerous line used to assess normal cell response to a drug, and the cancer line used to measure the tumour-killing potential of the drug being tested.
The Tallaght group has already had some success with the coumarin derivatives. "We have come up with a range of coumarin compounds that have the ability to leave the non-cancerous cells viable but kill off the cancer cells." They are now involved in understanding how it works, discovering "what it is about the cancer cell that allows coumarin to target it".
This is where the intracellular signalling comes in. Special enzymes called kinases are central to this process. They are involved in cell division, internal characteristics and cell death. The coumarin derivatives all hit particular kinases.
"Generally the kinases act in a cascade," says Egan.
They bind with one another and interact in a highly structured and coordinated way.
The drug interrupts this cascade to such a degree that controlled cell death - apoptosis - is triggered and the cancer cell dies.
They are using tagged antibodies that attach to specific kinases so they can understand how the process works, and whether a gene responsible for a kinase has been switched on or off.
The in vitro tests will identify promising drugs but extensive further testing will be required before the researchers know if they have discovered something valuable.