A team led by Associate Professor Jun-Ping Liu, from the Department of Immunology, has identified two proteins that are involved in stopping the gene from producing a protein called telomerase that is essential if cancer cells are to proliferate.

Telomerase plays a key role in controlling the life span of cells by modifying structures called telomeres that are found at the end of chromosomes.

Although it is involved in tumour development, telomerase is also found in modest quantities in most cells. It is plentiful in stem cells where it keeps the telomeres long, allowing the cells to keep dividing without limit which is necessary for the repair of damaged and worn out tissues throughout the human body.

However, studies have shown that telomerase also plays a key role in the formation of cancerous tumours. "It's the best indicator of cancer - 85 per cent better than any other tumour marker," Associate Professor Liu said. "What's more, telomerase is not associated with benign tumours; it's a marker for malignant tumours only.

"If we can control the production of telomerase we can prevent the immortality of cancer cells and therefore cancer formation."

Associate Professor Liu and his colleagues have been investigating breast cancer cells to identify the molecular signalling that is required to turn on, and also inhibit, the gene that produces telomerase. They have found two proteins Smad3 and c-Myc that are involved in turning off telomerase production. Their findings are published in the current issue of the Journal of Biological Chemistry.

"It's significant to find inhibitors of telomerase and we have found, for the first time, the pathway that inhibits telomerase in human cells," Associate Professor Liu said.

"This reveals an important mechanism for developing anti-cancer agents that mimic these proteins and thereby inhibit the production of telomerase. "

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To gauge the effectiveness of a dietary treatment, the researchers had special rat chow manufactured that incorporated a fairly large quantity of alpha-TEA into the food. They then tested the chow as a cancer preventive and as a cancer treatment.

For the prevention study, the mice ate alpha-TEA chow starting on the same day that they were injected with rodent mammary tumor cells known to spread quickly to the lungs and bones. The mice were allowed to eat as much food as they wanted, and at the end of 29 days, the average tumor volume was reduced by 6.7-fold, compared to control mice who had not been fed alpha-TEA.

In the therapy experiment, mice started eating alpha-TEA chow 11 days after tumors were implanted, and in the experimental group, there was a 3.6-fold reduction in average tumor volume compared to control mice, Akporiaye said.

In both preventive and therapeutic studies, mice fed alpha-TEA chow had a 4.8-fold reduction in the number of tumors that had spread to the lungs, compared to control mice. "The results were very impressive," he said. "The chow was very effective in slowing down the growth rate of the tumor and significantly reducing metastases."

The alpha-TEA diet produced no visible adverse side effects, not even weight loss, Akporiaye said.

"The combined characteristics of ease of delivery, relevance of route of delivery and selectivity for killing tumor cells suggest that dietary alpha-TEA may be useful for treating metastatic breast cancer," he said.

The researchers are now testing the effect of reduced doses of alpha-TEA in the chow and plan to test the synthetic vitamin in combination with dendritic cell immunotherapy. "When you kill tumor cells, they release antigens that can be picked up by specialized cells that stimulate the immune system,, and this two-step process could provide a longer lasting outcome," Akporiaye said.

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