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Green tea targets cancer cell migration


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Green tea targets cancer cell migration

[February 15, 2009]

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Green tea has been drunk for thousands of years in China and is recognised for its healthy properties. More recently, the active components have been identified as polyphenols, a set of compounds that are natural antioxidants and include the catechin family. During modern studies of the protective effects of green tea, it has been shown to be effective against several types of cancer, including lung cancer, the leading cancer killer of the Western world.

Lung cancer is difficult to cure because it can spread very quickly to other organs in the body to produce secondary or metastatic tumours. It has accounted for more than 160,000 deaths in 2007 in the US alone. So, there has been great interest in the potential chemopreventive properties of green tea, although its mechanism of action is poorly understood.

One group of scientists from the University of California, Los Angeles, has reported in separate studies that a green tea extract increases the levels of annexin I and induces remodelling of the protein actin, which increases cell adhesion, so reducing cell motility. Now, that same group has undertaken a wide ranging proteomics study to try and identify the molecular targets for motility inhibition in human lung cancer cells following treatment with a green tea extract that consisted primarily of catechins.

Joseph Loo and colleagues from various departments at the university, with Frederick Li from the Dana-Farber Cancer Institute in Boston, first carried out some preliminary experiments on the dose effects of the extract on A549 lung cancer cells. They found that cell proliferation was inhibited by 19, 41 and 82% at concentrations of 20, 40 and 80 µg/mL extract but the length of treatment had no effect. So, the positive action of green tea extract was confirmed.

For the main part of the study, the lung cancer cells were incubated for 24 hours with the extract. Proteins were extracted from the lysed cells by standard techniques and separated by 2D gel electrophoresis, comparing the gels of treated and untreated cells. A total of more than 600 protein spots were resolved on each gel and 62 showed significant changes in expression. These were cut from the gel and digested with trypsin for analysis by LC/MS with electrospray ionisation and identification by searching the SwissProt homo sapiens database.

This led to 39 identified proteins, 14 of which were deemed by statistical analysis to show a 2-fold dose-responsive increase or decrease in abundance following treatment. They were involved in calcium binding, cell cycle regulation, metabolism, detoxification, gene regulation and cytoskeletal/motility.

The levels of annexin I were increased, as expected, but when its expression was blocked by using small interfering RNA (siRNA) the decrease in cell motility was not completely removed, implicating other proteins too. One candidate is lamins A/C, whose expression was increased dose-dependently by green tea treatment. Further siRNA studies confirmed the likely involvement of lamins A/C in the inhibition of cell motility.

Lamins A/C were located in the nucleoplasm and the cytoplasm, although the mechanism of localisation remains unclear. However, "the data clearly indicate that green tea extract-inhibited A549 cell proliferation and induced apoptosis that is accompanied by lamin A/C degradation." It is possible that annexin I and lamins A/C join forces to modulate cell motility.

These may not be the only proteins involved in the regulation of apoptosis, say the team, and other proteins may also be implicated. Of the specific 14 proteins recognised in this study, annexin II and 14-3-3 protein are strong candidates for participation, based on their known activities.

Knowing the proteins involved in the growth, motility and apoptosis of A549 lung cancer cells should help to understand the multiple activities of green tea extract against the spread and growth of tumours.

Related links:

•Proteomics 2009, 9, 757-767: "Effects of green tea extract on lung cancer A549 cells: Proteomic identification of proteins associated with cell migration"

Article by Steve Down

The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.

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