New insight into green tea's action on bladder cancer

Green tea extract is able to target cancer cells while leaving healthy cells alone, researchers have found for the first time, adding further support to its potential as a cancer prevention agent.

The UCLA team has also uncovered more about how green tea extract counteracts the development of cancer. This could allow researchers to work out which people could benefit from the extract.

About 500 metric tons of green tea extract were sold in Europe during 2003, mostly for use in beverages and cosmetics. But the extracts are set to be increasingly used in supplements as evidence of their benefits gain weight.

Numerous epidemiological and animal studies have suggested that green tea extract provides strong anti-cancer effects in several human cancers, including bladder cancer.

In 2003 US researchers found that the active ingredient in green tea, epigallocatechin-3-gallate (EGCG), blocked the growth of bladder tumours in rats.

Green tea extract has been shown to induce death in cancer cells, as well as inhibiting the development of an independent blood supply that cancers develop so they can grow and spread.

In the new study on bladder cancer cell lines, scientists demonstrated that the plant extract interrupts a process that is crucial in allowing bladder cancer to become invasive and spread to other areas of the body.

The findings, published in the 15 February issue of Clinical Cancer Research, "add a new dimension in understanding the mechanisms of green tea extract," said senior author JianYu Rao.

The researchers have found that green tea extract affects actin remodeling, an event associated with cell movement. For cancer to grow and spread, the malignant cells must be able to move in order to invade other healthy cells and eventually other organs.

The cells rely on actin remodeling, which is carefully regulated by complex signaling pathways, including the Rho pathway. By inducing Rho signaling, the green tea extract made the cancer cells more mature and made them bind together more closely - a process called cell adhesion. Both the maturity of the cells and the adhesion inhibited the mobility of the cancer cells, Rao said.

"In effect, the green tea extract may keep the cancer cells confined and localized, where they are easier to treat and the prognosis is better," Rao said. "Cancer cells are invasive and green tea extract interrupts the invasive process of the cancer."

Rao cautioned that his study was conducted in a carefully controlled cell line environment and that more research needs to be done to discover exactly how green tea extract functions as a cancer fighter. The next phase of his research will analyze urine from bladder cancer patients to determine which subset of patients would benefit most from taking green tea extract.

Researchers will be looking for specific biomarkers associated with actin remodeling and activation of the Rho signaling pathway.

"We're hoping the results from these studies will tell us who will best benefit from the agent," Rao said.

He explained that knowing how it works to inhibit the development of cancer will allow researchers to "figure out more precisely which bladder cancer patients might benefit from taking it".

Bladder cancer is the fourth most common cancer in men in the UK and the 10th most common in women. In the US about 56,000 new cases are diagnosed each year. The disease can be difficult to detect in the early, most treatable stages. When not found early, the tumours can be aggressive, and more than half of patients with advanced cancers experience recurrences.

UCLA researchers are also currently seeking hundreds of former smokers who have had bladder cancer for a clinical trial studying whether green tea extract prevents recurrence - one of the first studies to test the agent on cancer patients. About half of all bladder cancers are believed to be related to cigarette smoking.

They are also aiming to develop new biomarker tests to help predict who will get bladder cancer, discover the molecular profile of the disease to identify those most at risk and create a tumour bank to aid research.

"In the end, both studies will help us achieve our goal - to decrease bladder cancer occurrence and develop molecular profiles that tell us who is most at risk."

Epidemiological studies have also shown selenium and vitamin E to decrease the risk of bladder cancer.