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Wednesday 28 October 2009; British Journal of Cancer Press Release

MOLECULES found in curry ingredients have been shown to kill oesophageal cancer cells in the laboratory, reveals research published in the British Journal of Cancer today (Wednesday).

Scientists based at the Cork Cancer Research Centre treated oesophageal cancer cells with curcumin – a chemical found in the curry spice tumeric.

They found that curcumin started to kill cancer cells within 24 hours. The cells also began to digest themselves.

The results additionally showed that curcumin kills cells by triggering lethal cell death signals.

Dr Sharon McKenna, lead study author, based at the Cork Cancer Research Centre, University College Cork, said:

“These exciting results suggest scientists could develop curcumin as a potential anti-cancer drug to treat oesophageal cancer.

“Scientists have known for a long time that natural compounds have the potential to treat faulty cells that have become cancerous and we suspected that curcumin might have therapeutic value. Dr Geraldine O’Sullivan-Coyne, a medical researcher in our lab had been looking for new ways of killing resistant oesophageal cancer cells. She tested curcumin on resistant cells and found that they started to die using an unexpected system of cell messages.”

Normally, faulty cells die by committing programmed suicide – or apoptosis – which occurs when proteins called caspases are ‘switched on’ in cells. But these cells showed no evidence of suicide and the addition of a molecule that inhibits caspases and stops this ‘switch being flicked’, made no difference to the number of cells which died. This suggested that curcumin attacked the cancer cells using an alternative cell signalling system.

Each year around 7,800 people are diagnosed with oesophageal cancer in the UK - around 160 of these are in Northern Ireland. Less than 20 per cent of people survive oesophageal cancer beyond five years. It is the sixth most common cause of cancer death and accounts for around five per cent of all UK cancer deaths.

Dr Lesley Walker, director of cancer information at Cancer Research UK, said: “This is interesting research which opens up the possibility that natural chemicals found in tumeric could be developed into new treatments for oesophageal cancer.

“Rates of oesophageal cancer rates have gone up by more than a half since the 70s and this is thought to be linked to rising rates of obesity, alcohol intake and reflux disease so finding ways to prevent this disease is important too.”

Molecular Diagnostics

British Journal of Cancer (2009) 101, 1585–1595. doi:10.1038/sj.bjc.6605308 www.bjcancer.comPublished online 6 October 2009

Curcumin induces apoptosis-independent death in oesophageal cancer cells

Background:Oesophageal cancer incidence is increasing and survival rates remain extremely poor. Natural agents with potential for chemoprevention include the phytochemical curcumin (diferuloylmethane). We have examined the effects of curcumin on a panel of oesophageal cancer cell lines.

Methods:MTT (3-(4,5-dimethyldiazol-2-yl)-2,5 diphenyl tetrazolium bromide) assays and propidium iodide staining were used to assess viability and DNA content, respectively. Mitotic catastrophe (MC), apoptosis and autophagy were defined by both morphological criteria and markers such as MPM-2, caspase 3 cleavage and monodansylcadaverine (MDC) staining. Cyclin B and poly-ubiquitinated proteins were assessed by western blotting.

Results:

Curcumin treatment reduces viability of all cell lines within 24 h of treatment in a 5–50 μM range. Cytotoxicity is associated with accumulation in G2/M cell-cycle phases and distinct chromatin morphology, consistent with MC. Caspase-3 activation was detected in two out of four cell lines, but was a minor event. The addition of a caspase inhibitor zVAD had a marginal or no effect on cell viability, indicating predominance of a non-apoptotic form of cell death. In two cell lines, features of both MC and autophagy were apparent. Curcumin-responsive cells were found to accumulate poly-ubiquitinated proteins and cyclin B, consistent with a disturbance of the ubiquitin–proteasome system. This effect on a key cell-cycle checkpoint regulator may be responsible for the mitotic disturbances and consequent cytotoxicity of this drug.

Conclusion:Curcumin can induce cell death by a mechanism that is not reliant on apoptosis induction, and thus represents a promising anticancer agent for prevention and treatment of oesophageal cancer.

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