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Green tea compound found to kill oral cancer cells

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A compound found in green tea can kickstart a process that kills oral
cancer cells while leaving healthy cells alone, lab tests have revealed.
 
Led by Joshua Lambert, associate professor of food science and
co-director of Pennsylvania State University’s Centre for Plant and
Mushroom Foods for Health, researchers have watched as the compound
epigallocatechin-3-gallate (EGCG) – the most abundant antioxidant in
green tea – triggers a cycle of damage in the mitochondria of cancer
cells, which essentially causes them to disintegrate from the
inside-out.
“EGCG is doing something to damage the mitochondria
and that mitochondrial damage sets up a cycle causing more damage, and
it spirals out, until the cell undergoes programmed cell death,” says Lambert in a press release.
“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.”
These reactive
oxygen species – also known as free radicals – are oxygen-containing
molecules that, if allowed to accumulate in numbers that overwhelm the
cell’s antioxidant defence, will cause oxidative stress.
If left untreated, oxidative stress can damage all components of the
cell, including the proteins, lipids, and DNA, and lead to the
development of all kinds of devastating diseases including cancer,
Parkinson’s and Alzheimer’s disease, infections, and chronic fatigue
syndrome.

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While the cancer cell is undergoing oxidative stress thanks to the
green tea compound EGCG, the researchers found that the damage to the
mitochondria grows progressively worse. While at the same time, the
cell’s expression of its antioxidant genes – which are supposed to fight
the reactive oxygen species – is reduced. This means the cancer cell is
switching off its main defence mechanism while EGCG is further
weakening it with oxidative stress.
And curiously, the devastating
effects on cancer cells were not seen in normal, healthy cells. Quite
the opposite – the researchers found that the compound actually
increased what’s known as the mitochondrial membrane potential, which is
essential for a healthy metabolism within the cell.
The team
figured this out by growing normal, healthy cells and oral cancer cells
in petri dishes, and then exposing them to EGCG. They say the amount
they used was equivalent to how much would end up in your saliva after
chewing green-tea gum. The cells were then periodically monitored for
oxidative stress and signs of defensive antioxidant response.
Through this process, they identified the protein sirtuin 3 (SIRT3),
as playing a crucial role in 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 Lambert.
While
EGCG significantly reduced protein and messenger RNA levels – the
molecules that carry DNA codes in the cell’s nucleus to sites of protein
synthesis – of SIRT3 in oral cancer cells, the researchers found that
it had no effect on the SIRT3 expression in normal cells.
The team published their results in the online issue of Molecular Nutrition and Food Research.
Lambert says the results tie in to previous findings of separate
studied, where green tea compounds have been shown to treat and prevent
oral cancer in animal studies. 
In 2014, it was estimated
that 42,440 new cases and 8,390 deaths from oral cancer will occur in
the US this year. Smokers are the most vulnerable group, because tobacco
is known to induce genetic changes that irreversibly increase the risk
of developing the disease. 
The team would now like to do their
own studies on animals in the lab, to see if the effects they observed
in the petri dishes can be replicated in a living creature. 
“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,” said Lambert. “But you don’t see these sorts of side effects with green tea consumption.”

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