Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Breast cancer drug beats superbug

13.10.2015

Tamoxifen helps white blood cells clear multidrug-resistant bacteria in lab and mouse studies

Researchers at University of California, San Diego School of Medicine and Skaggs School of Pharmacy and Pharmaceutical Sciences have found that the breast cancer drug tamoxifen gives white blood cells a boost, better enabling them to respond to, ensnare and kill bacteria in laboratory experiments. Tamoxifen treatment in mice also enhances clearance of the antibiotic-resistant bacterial pathogen MRSA and reduces mortality.


Neutrophils produce bacteria-ensnaring NETs (shown in blue/green) in response to Tamoxifen treatment.

Credit: UC San Diego School of Medicine

The study is published October 13 by Nature Communications.

"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," said senior author Victor Nizet, MD, professor of pediatrics and pharmacy. "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."

Tamoxifen targets the estrogen receptor, making it particularly effective against breast cancers that display the molecule abundantly. But some evidence suggests that tamoxifen has other cellular effects that contribute to its effectiveness, too. For example, tamoxifen influences the way cells produce fatty molecules, known as sphingolipids, independent of the estrogen receptor. Sphingolipids, and especially one in particular, ceramide, play a role in regulating the activities of white blood cells known as neutrophils.

"Tamoxifen's effect on ceramides led us to wonder if, when it is administered in patients, the drug would also affect neutrophil behavior," said first author Ross Corriden, PhD, project scientist in the UC San Diego School of Medicine Department of Pharmacology.

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 toward and phagocytosing, or engulfing, bacteria. Tamoxifen-treated neutrophils also produced approximately three-fold more neutrophil extracellular traps (NETs), 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 estrogen receptor had no effect, suggesting that tamoxifen enhances NET production in a way unrelated to the estrogen receptor. Further studies linked the tamoxifen effect to its ability to influence neutrophil ceramide levels.

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 (methicillin-resistant Staphylococcus aureus), a "superbug" of great concern to human health. They treated the mice again with tamoxifen or the control one and eight hours after infection and monitored them for five days.

Tamoxifen significantly protected mice -- none of the control mice survived longer than one day after infection, while about 35 percent of the tamoxifen-treated mice survived five days. Approximately five times fewer MRSA were collected from the peritoneal fluid of the tamoxifen-treated mice, as compared to control mice.

There are two caveats, the researchers said. First, while tamoxifen was effective against MRSA in this study, the outcome may vary with other pathogens. That's because several bacterial species have evolved methods for evading NET capture. 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.

"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," Nizet said.

Tamoxifen is taken daily by hundreds of thousands of patients worldwide for the treatment of estrogen receptor-positive breast cancer. The World Health Organization considers tamoxifen an "essential medicine," due to its cost-effectiveness and safety profile. According to the breast cancer organization Susan G. Komen, generic tamoxifen cost patients about $100 per month in 2010.

Tamoxifen is not the only drug prescribed for other indications that just happen to also boost neutrophil activity. In 2010, Nizet and team reported that cholesterol-lowering statins also enhance NET formation. That study can be found at http://www.ncbi.nlm.nih.gov/pubmed/21075355

###

Co-authors of this study include Andrew Hollands, Joshua Olson, Jaclyn Derieux, Justine Lopez, John T. Chang, David J. Gonzalez, all of UC San Diego.

This research was funded, in part, by the National Institutes of Health (grants HD071600, AI057153, AI052453 and OD008469).

Media Contact

Heather Buschman
hbuschman@ucsd.edu
619-543-6163

 @UCSanDiego

http://www.ucsd.edu 

Heather Buschman | EurekAlert!

More articles from Health and Medicine:

nachricht Penn studies find promise for innovations in liquid biopsies
30.03.2017 | University of Pennsylvania School of Medicine

nachricht 'On-off switch' brings researchers a step closer to potential HIV vaccine
30.03.2017 | University of Nebraska-Lincoln

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: A Challenging European Research Project to Develop New Tiny Microscopes

The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.

To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

'On-off switch' brings researchers a step closer to potential HIV vaccine

30.03.2017 | Health and Medicine

Penn studies find promise for innovations in liquid biopsies

30.03.2017 | Health and Medicine

An LED-based device for imaging radiation induced skin damage

30.03.2017 | Medical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>