25th August 2011, 9:11am
Antidepressants can cut cancer risk

 
UK research points to 'Achilles heel' in cancer cells which could pave way for new treatments

Antidepressants commonly prescribed to treat depression and other psychiatric disorders can significantly reduce people's chances of developing certain kinds of cancer and could present a blueprint for the development of new anti-cancer drugs.

A study of more than 90,000 patients from across the UK found that those who were taking tricyclic antidepressants had a significantly lower incidence of colorectal cancer and glioma (a major type of brain tumour) than those who were not taking the drugs.

Colorectal cancer is one of the most common forms of cancer in the developed world. Glioma is less common but treatment options are very limited and prognosis is poor, particularly in advanced stages of the illness.

The findings of Dr Tim Bates (University of Lincoln and New-Use Therapeutics Limited),  Dr Alex Walker and Dr Tim Card (both University of Nottingham) and Professor Ken Muir (University of Warwick) points to an "Achilles heel" in cancer cells which could provide a basis for the development of new drug treatments. This vulnerability is in sub-cellular compartments know as mitochondria - the ‘boilerhouse’ of the cell which produces the chemical energy needed to perform essential functions such as muscle contraction and nerve conduction.

Their study, funded with a grant from the Medical Research Council, involved analysing data from the General Practice Research Database - an anonymised database of routinely collected patient records from GP practices across the UK which is the largest resource of its kind in the world. During this analysis 31,593 cancer patients were identified from the database and then matched to a large control group of 61,591 patients without cancer. The cases and controls were adjusted for age and gender, as well as other factors such as smoking, body mass index and alcohol use, so that these factors would not bias the results.

The groups of patients and controls were then investigated for incidences of several common cancers of the West including breast, colorectal, lung and prostate cancer as well as brain tumours, including glioma.

Highly statistically significant trends were found which indicate that use of tricyclic antidepressants reduce the risk of developing glioma and colorectal cancer. The size of the effects was greater with higher doses and longer duration of exposure to the drugs, and thus the effects were both dose-dependent and time-dependent.

Tricyclic antidepressants were shown to reduce the chances of developing glioma by between 41% and 64%, depending on the dose and length of time for which the drugs were taken. The effect on colorectal cancer was somewhat less, with between a 16-21% reduction in risk of getting the disease.

The anti-cancer effect was specific to glioma and colorectal cancer, as the chances of developing the other types of cancer that were investigated were not affected.

Dr Bates said although it was not realistic that tricyclic antidepressants could be widely prescribed to prevent cancer, given their side effects, it was possible that they could benefit patients identified through DNA screening as being at heightened risk of developing specific cancers.

More significantly, the findings offer the basis for a new approach to the prevention and treatment of cancer through the development of anti-mitochondrial drugs which inhibit the growth of cancer cells without harming normal cells.

Dr Bates said: "The cancer prevention action of these drugs may translate into one that is also useful in treating glioma, both in adults and in children, and colorectal cancer. Our group is currently investigating this possibility, and will shortly be in discussions with major charities, funding bodies and industry with a view to extending this incredibly important research work collaboratively, both here at the University of Lincoln, and at other centres in the UK and abroad.”

The research, published earlier this year in the British Journal of Cancer, builds on a previous study funded by the Samantha Dickson Brain Tumour Trust which showed that certain antidepressants inhibit mitochondria directly, resulting in a form of “cell suicide” known as programmed cell death or apoptosis.

Dr Bates concluded: “Development of drugs that modulate mitochondrial function may seem counter-intuitive as mitochondria provide the majority of the cell’s energy, but as cancer mitochondria are biochemically different from mitochondria in normal non-cancer cells, they represent an Achilles heel. It is likely this will lead to the development of new drug treatments for a variety of conditions including cancer, Alzheimer’s, Diabetes and other disorders.”

The paper ‘Tricylic antidepressants and the incidence of certain cancers: a study using the GPRD’ by AJ Walker, T Card, TE Bates and K Muir was published in the British Journal of Cancer 2011 Jan 4;104(1):193-7. Epub 2010 Nov 16. The research was funded by a Medical Research Council (MRC) grant to Dr Bates and Prof Muir.
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