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A green approach to cancer research
Understanding what turns on and turns off apoptosis or cell suicide
promises to provide a new range of tools for fighting cancer.
Dr Mark Hampton, an HRC Sir Charles Hercus Health Research Fellowship
recipient, is part of the Free Radical Research Group at the Christchurch
School of Medicine and Health Sciences.
Apoptosis should be switched on when something goes wrong in a
cell, such as when it gets damaged or begins to grow out of control,
Dr Hampton explains. “Unfortunately in a number of cancer cells this
pathway gets switched off, and the cell continues to grow.”
Dr Mark Hampton
Key words:
– cancer, apoptosis, drug resistance,
isothiocyanates.
Key facts about cancer in
New Zealand:
– 7,674 New Zealanders died of
cancer in 1999, more than 20 every
day.
– a major cause of treatment failure
is the development of drug
resistance by cancer cells.
Aims of our research are to:
– characterise the ability of various
isothiocyanates to trigger
apoptosis in normal cells and
cancer cells
– discover what proteins are being
targeted by isothiocyanates, and
how this leads to the induction of
apoptosis.
What our research has found:
– phenethyl isothiocyanate (present
in watercress) is able to kill cancer
cells that are resistant to a range
of chemotherapeutic drugs
– a distinct set of thiol proteins are
modified in cancer cells treated
with isothiocyanates, and these
proteins are currently being
identified.
This resistance to apoptosis also complicates the task of oncologists who
find cancer cells can become resistant to chemotherapy as well.
The key for Dr Hampton and his colleagues in the Free Radical Research
Group is to find compounds that can turn apoptosis on again. They now
have a particularly promising group of compounds called isothiocyanates,
which are derived from cruciferous vegetables such as watercress, broccoli
and wasabi. Isothiocyanates are responsible for the pungency and peppery
flavour of these plants.
It is already known that isothiocyanates can protect against cancer, and that
they can trigger apoptosis. But Dr Hampton’s team has also discovered that
one of these compounds can kill drug-resistant cancer cells, and sensitise
them to other agents that trigger apoptosis.
They intend to look at a range of different isothiocyanates to try and
discover the chemical features important for promoting apoptosis. They
will also look at the efficacy of crude extracts of cruciferous vegetables to
see if they do the same thing. The ability to drive apoptosis may contribute
to the cancer preventive properties of these plants.
The research team is also studying what is happening at a molecular level
inside cells. The goal is to identify the targets of isothiocyanates, and
understand how they promote apoptosis in cells. Dr Hampton believes
that specialized thiol proteins inside cells are able to control processes like
apoptosis and the team has developed a proteomic technique to monitor
changes in all the thiol proteins in a cell.
“The technique will allow us to identify the molecular targets of the
isothiocyanates. This fundamental knowledge will be crucial in working
out how isothiocyanates promote apoptosis in cancer cells, and provide a
foundation for developing them or related products for use in the clinic.”
This research is funded by the Health Research Council of New Zealand, and has
also received funding from the Cancer Society of New Zealand, the Marsden Fund,
the Canterbury Medical Research Foundation and the University of Otago.
HRC39 2004
Level 3, 110 Stanley Street, Auckland PO Box 5541,
Wellesley Street, Auckland, NZ
Telephone 64 9 303 5200 Facsimile 64 9 377 9988
Website www.hrc.govt.nz
Health Research Council of New Zealand
Te Kaunihera Rangahau Hauora o Aotearoa