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Could a breast cancer drug wipe out MRSA in hospitals?

  • Drug tamoxifen blocks oestrogen which stops breast tumours growing
  • But it also gives white blood cells a boost, helping them kill bacteria
  • Tamoxifen-treated white blood cells produced more traps to engulf germs
  • Five times fewer MRSA bacteria were found in mice treated with the drug 

By Madlen Davies for MailOnline

Published: 06:11 EST, 13 October 2015 | Updated: 08:30 EST, 13 October 2015

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A common breast cancer drug could finally wipe out a notorious superbug found in hospitals, new research suggests.

The study revealed tamoxifen helps white blood cells in the body clear the bacteria MRSA.

US researchers found that tamoxifen gives white blood cells a boost, better enabling them to ensnare and kill bacteria in laboratory experiments and those on mice.

And the study showed tamoxifen treatment in mice also enhanced clearance of the MRSA which had become resistant to antibiotics, and reduced death from it.

The notorious MRSA superbug (pictured) could be wiped out with the commonly-prescribed breast cancer drug tamoxifen, scientists announced today 

The notorious MRSA superbug (pictured) could be wiped out with the commonly-prescribed breast cancer drug tamoxifen, scientists announced today 

Tamoxifen is taken daily by hundreds of thousands of patients worldwide for the treatment of breast cancer.

The study's senior author, Professor Victor Nizet, of the University of California San Diego School of Medicine, said: 'The threat of multidrug-resistant bacterial pathogens is growing, yet the pipeline of new antibiotics is drying up.

'We need to open the medicine cabinet and take a closer look at the potential infection-fighting properties of other drugs that we already know are safe for patients.

'Through this approach, we discovered that tamoxifen has pharmacological properties that could aid the immune system in cases where a patient is immunocompromised or where traditional antibiotics have otherwise failed.'

To grow and reproduce, breast cancer cells require the female hormone oestrogen.

Tamoxifen binds to oestrogen receptors in breast cancer cells, blocking oestrogen from reaching them.

This means the cancer either grows more slowly or stops growing altogether.

But, independent of the oestrogen receptor, the drug also influences the way cells produce fatty molecules, known as sphingolipids.

One sphingolipid in particular, ceramide, plays a role in regulating the activities of white blood cells known as neutrophils.

The study's author, Dr Ross Corriden, also of the University of California San Diego School of Medicine, said: 'Tamoxifen's effect on ceramides led us to wonder if, when it is administered in patients, the drug would also affect neutrophil behaviour.'

Tamoxifen is taken daily by hundreds of thousands of patients worldwide for the treatment of breast cancer

Tamoxifen is taken daily by hundreds of thousands of patients worldwide for the treatment of breast cancer

To test their theory, the researchers incubated human neutrophils with tamoxifen. 

Compared to untreated neutrophils, they found that tamoxifen-treated neutrophils were better at moving towards and devouring bacteria.

Tamoxifen-treated neutrophils also produced approximately three times more neutrophil extracellular traps (NETs).

These are a mesh of DNA, antimicrobial peptides, enzymes and other proteins that neutrophils spew out to ensnare and kill pathogens.

Treating neutrophils with other molecules that target the oestrogen receptor had no effect, suggesting that tamoxifen enhances NET production in a way unrelated to the oestrogen receptor. 

Further studies linked the tamoxifen effect to its ability to influence ceramide levels, which affect neutrophils.

The team also tested tamoxifen's immune-boosting effect in a mouse model. 

One hour after treatment with tamoxifen or a control, the researchers infected mice with MRSA. 

They treated the mice again with tamoxifen or the control one and eight hours after infection and monitored them for five days.

Tamoxifen blocks oestrogen production in breast tissue - and some breast cancer cells require oestrogen to grow. Therefore, using tamoxifen to block oestrogen production can help prevent the cancer spreading

Tamoxifen blocks oestrogen production in breast tissue - and some breast cancer cells require oestrogen to grow. Therefore, using tamoxifen to block oestrogen production can help prevent the cancer spreading

Tamoxifen significantly protected the mice - none of the control mice survived longer than one day after infection, while about 35 per cent of the tamoxifen-treated mice survived five days.

Around five times fewer MRSA bacteria were collected from the peritoneal fluid of the tamoxifen-treated mice, compared to control mice. 

Professor Nizet said: 'While known for its efficacy against breast cancer cells, many other cell types are also exposed to tamoxifen.

'The "off-target effects" we identified in this study could have critical clinical implications given the large number of patients who take tamoxifen, often every day for years.'

However, the researchers said that while tamoxifen was effective against MRSA in this study, the outcome may vary with other bacteria.

Several bacterial species have evolved methods for evading NET capture, they said.

Second, in the absence of infection, too many NETs could be harmful.

Some studies have linked excessive NET production to inflammatory disease, such as vasculitis and bronchial asthma, they added.

The study was published in the journal Nature Communications. 

 

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