Source: www.dailymail.co.uk
Author: Lizzie Parry
A compound in green tea has been found to kill mouth cancer cells while leaving healthy cells undamaged. While it was known the drink could help fight the disease, scientists say they have now worked out why. The breakthrough involved identifying the process by which the substance attacks cancer cells. This, it is hoped, will lead to new treatments for oral cancer, as well as other forms of the disease.
Scientists at Penn State University, in the US, explored the specific mechanism by which the green tea compound is able to target the diseased cells. Earlier studies have shown that epigallocatechin-3-gallate (EGCG), a compound found in green tea, killed mouth cancer cells without harming normal cells. But researchers did not understand the reasons behind the substance’s ability to kill the cancer cells. Scientists now believe EGCG may trigger a process in the mitochondria – the powerhouse of a cell that produces energy – that leads to cell death.
Professor Joshua Lambert, a specialist in food science and co-director of Penn State’s Center for Plant and Mushroom Foods for Health, said: ‘EGCG is doing something to damage the mitochondria.
‘That mitochondrial damage sets up a cycle causing more damage and it spirals out, until the cell undergoes programmed cell death.
‘It looks like EGCG causes the formation of reactive oxygen species in cancer cells, which damages the mitochondria, and the mitochondria responds by making more reactive oxygen species.’
Reactive oxygen species are chemically reactive molecules containing oxygen. They play an important role in cell signalling and homeostatsis – the control of internal conditions including temperature. When reactive oxygen species levels increase dramatically, it can cause significant damage to cell structures – this is known as oxidative stress. As this mitochondrial demise continues, the cancer cell also reduces the expression of antioxidant genes, further lowering its defences.
‘So, it’s turning off its mechanism of protection at the same time that EGCG is causing this oxidative stress,’ Professor Lambert added.
His team discovered the EGCG did not cause the same reaction in normal cells. In fact, the compound appeared to increase the healthy cell’s protective capabilities.
The researchers studied normal human oral cells, alongside human oral cancer cells, to determine how the compound was targeting the cancer cells differently to those healthy tissues. They grew the normal and cancer cells on petri dishes, before exposing them to EGCG – the major polyphenol found in green tea. They used concentrations of the compound typically found in the saliva after a person chews green tea gum. At specific times the scientists collected the cells to check for oxidative stress and signs of antioxidant response.
Professor Lambert, said: ‘We also took a lot of pictures, so we could use fluorescent dyes that measure mitochondrial function and oxidative stress and actually see these things develop.’
His team identified a protein called sirtuin 3 (SIRT3) is critical to the process.
‘It plays an important role in mitochondrial function and in antioxidant response in lots of tissues in the body, so the idea that EGCG might selectively affect the activity of sirtuin 3 in cancer cells – to turn it off – and in normal cells – to turn it on – is probably applicable in multiple kinds of cancers,’ said Professor Lambert.
This study builds on past research into how the compound affects oral cancer, a disease expected to kill more than 8,000 people in the US this year.
‘We’ve published one paper previously just looking at the effect of these green tea polyphenols on oral cancer cells in cultures,’ said Professor Lambert.
‘And there have been other papers published using oral cancer cells and at least a couple of animal model studies that have looked at oral cancer and prevention of oral cancer.’
He said the next step would be to study the mechanism in animals. If those tests and human trials were then successful, the scientists hope to create cancer treatments that are as effective as current ones, but without the harmful side effects.
Professor Lambert added: ‘The problem with a lot of chemotherapy drugs – especially early chemotherapy drugs – is that they really just target rapidly dividing cells, so cancer divides rapidly, but so do cells in your hair follicles and cells in your intestines, so you have a lot of side effects.
‘But you don’t see these sorts of side effects with green tea consumption.’
The study, supported by the American Institute for Cancer Research, was published in the online issue of Molecular Nutrition and Food Research.
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