AUG 31, 2016 08:59 AM PDT

Salmonella School Scientists on How to Thwart Cancer

WRITTEN BY: Xuan Pham
Cancer cells know when they’re being attacked. And one of their best counterattack strategies is to pump the chemotherapy drugs out of their cells. Now researchers at the University of Massachusetts Medical School say they can potentially thwart cancer’s defenses with nanoparticles that mimic the bacterium Salmonella.  

On the surface of some cancer cells, membrane proteins called P-glycoprotein (P-gp) act like funnel chutes that rid the cells of any toxins. This is bad news for cancer patients, as the presence of these proteins on cancer cells can compromise the efficacy of chemotherapy treatments.

Serendipitously, researchers noted that Salmonella – the bacteria that’s notorious for food poisonings – appear to reduce the level of P-gp in cells. "While trying to understand how Salmonella invades the human host, we made this other observation that may be relevant to cancer therapeutics and multidrug resistance," said Beth McCormick, lead study author.

Could they co-opt the bacteria’s strategy and ultimately reduce chemotherapy resistance? Indeed, through several experiments, McCormicks’ team identified a key protein in Salmonella that seemed to influence the level of P-gp. That protein is known as SipA. In cell cultures, adding SipA alone was enough to reduce P-pg membrane proteins in human colon cancer, breast cancer, bladder cancer, and lymphoma. This, in combination with chemotherapy drugs, showed that the cancer cells were more susceptible to the anticancer treatment and were less able to expel the drugs out of their system.

"Through millions of years of co-evolution, Salmonella has figured out a way to remove this transporter from the surface of intestinal cells to facilitate host infection," said Dr. McCormick. "We capitalized on the organism's ability to perform that function."
 

But, it is not possible to treat cancer by infecting people with Salmonella. Nor is it feasible to administer SipA as a single molecule agent, as this compound is unstable in the bloodstream. Therefore, the team went with the next best thing and combined their knowledge with nanotechnology – that is, they created gold nanoparticles that are fused with SipA.

In preliminary cellular experiments, the nanoparticles proved to be 100 times more effective than SipA alone in lowering P-gp levels. Furthermore, in mouse models of colon cancer and breast cancer, combining traditional chemotherapy with the nanoparticles resulted in slower and smaller tumor growths. This indicates the SipA nanoparticles act to boost the anticancer effects of the chemotherapy.

As encouraging as these results are, the team is still wary about other possible side effects of reducing P-gp in the entire system. Since P-gp is actually a way for normal cells to stay healthy, interfering with this mechanism could produce drastic unwanted side effects.  "We are not naïve about the complexity of the problem," said McCormick. "However, if we know more about the biology, we believe we can ultimately make a better drug."

Additional sources: National Cancer Institute
About the Author
  • I am a human geneticist, passionate about telling stories to make science more engaging and approachable. Find more of my writing at the Hopkins BioMedical Odyssey blog and at TheGeneTwist.com.
You May Also Like
OCT 18, 2019
Cell & Molecular Biology
OCT 18, 2019
Insight Into a DNA Damage Sensor That Orchestrates Repair
Simple cell functions like division or metabolism can lead to DNA damage, which can also occur because of normal exposure to the sun or noxious agents....
OCT 18, 2019
Cell & Molecular Biology
OCT 18, 2019
Revealing More About Aging on the Cellular Level
Our bodies are made up of trillions and cells, and millions of them die every day....
OCT 18, 2019
Cell & Molecular Biology
OCT 18, 2019
Investigating the Molecular Basis of Sex-related Differences in Cancer
There are sex-specific differences in the rate and lethality of various cancers....
OCT 18, 2019
Cancer
OCT 18, 2019
Not the fried food!
Stop! Put down those fries! Although we know that fried foods aren’t good for our health (though they sure do taste good!), new research from UMass A...
OCT 18, 2019
Immunology
OCT 18, 2019
New Observations of a Cancer Transcriptase
New research shows a transcriptase that helps time cell death varies in expression, and is unusually localized, in cancer cells.  The transcriptase, T...
OCT 18, 2019
Cancer
OCT 18, 2019
One third of women don't take advantage of free cancer screenings
Have you ever received a cancer screening? If you haven’t, you’re not alone. New research from King's College London and Queen Mary Univers...
Loading Comments...