Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Synthetic molecule makes cancer self-destruct

12.08.2014

Researchers from The University of Texas at Austin and five other institutions have created a molecule that can cause cancer cells to self-destruct by ferrying sodium and chloride ions into the cancer cells.

These synthetic ion transporters, described this week in the journal Nature Chemistry, confirm a two-decades-old hypothesis that could point the way to new anticancer drugs while also benefitting patients with cystic fibrosis.

Synthetic ion transporters have been created before, but this is the first time researchers have shown them working in a real biological system where transported ions demonstrably cause cells to self-destruct.

Cells in the human body work hard to maintain a stable concentration of ions inside their cell membranes. Disruption of this delicate balance can trigger cells to go through apoptosis, known as programmed cell death, a mechanism the body uses to rid itself of damaged or dangerous cells.

One way of destroying cancer cells would be to trigger this innate self-destruct sequence by skewing the ion balance in cells. Unfortunately, when a cell becomes cancerous, it changes the way it transports ions across its cell membrane in a way that blocks apoptosis.

Almost two decades ago, a natural substance called prodigiosin was discovered that acted as a natural ion transporter and has an anticancer effect.

Since then, it has been a "chemist's dream," said Jonathan Sessler, professor in The University of Texas at Austin's College of Natural Sciences and co-author of the study, to find "synthetic transporters that might be able to do exactly the same job, but better, and also work for treating diseases such as cystic fibrosis where chloride channels don't work."

Sessler and his collaborators, led by professors Injae Shin of Yonsei University and Philip A. Gale of the University of Southampton and King Abdulaziz University, were able to bring this dream to fruition.

The University of Texas members of the team created a synthetic ion transporter that binds to chloride ions. The molecule works by essentially surrounding the chloride ion in an organic blanket, allowing the ion to dissolve in the cell's membrane, which is composed largely of lipids, or fats. The researchers found that the transporter tends to use the sodium channels that naturally occur in the cell's membrane, bringing sodium ions along for the ride.

Gale and his team found that the ion transporters were effective in a model system using artificial lipid membranes.

Shin and his working group were then able to show that these molecules promote cell death in cultured human cancer cells. One of the key findings was that the cancer cell's ion concentrations changed before apoptosis was triggered, rather than as a side effect of the cell's death.

"We have thus closed the loop and shown that this mechanism of chloride influx into the cell by a synthetic transporter does indeed trigger apoptosis," said Sessler. "This is exciting because it points the way towards a new approach to anticancer drug development."

Sessler noted that right now, their synthetic molecule triggers programmed cell death in both cancerous and healthy cells. To be useful in treating cancer, a version of a chloride anion transporter will have to be developed that binds only to cancerous cells. This could be done by linking the transporter in question to a site-directing molecule, such as the texaphyrin molecules that Sessler's lab has previously synthesized.

The results were a culmination of many years of work across three continents and six universities.

"We have demonstrated that this mechanism is viable, that this idea that's been around for over two decades is scientifically valid, and that's exciting," said Sessler. "We were able to show sodium is really going in, chloride is really going in. There is now, I think, very little ambiguity as to the validity of this two-decades-old hypothesis."

The next step for the researchers will be to take the synthetic ion transporters and test them in animal models.

###

Sessler's co-authors are Sung-Kyun Ko (Yonsei University and Korea Research Institute of Bioscience and Biotechnology); Sung Kuk Kim, Andrew Share and Vincent Lynch (UT Austin); Jinhong Park and Wan Namkung (Yonsei University); Wim Van Rossom and Nathalie Busschaert (University of Southampton); Philip Gale (University of Southampton and King Abdulaziz University); and Injae Shin (Yonsei University). Sung-Kyun Ko and Sung Kuk Kim were the lead authors on this study. Sessler, Gale and Shin were the corresponding authors.

This work was supported by the National Creative Research Initiative program in South Korea; the Office of Basic Energy Sciences in the U.S. Department of Energy; and the Chemical Biology Research Center in the Korea Research Institute of Bioscience and Biotechnology.

Steve Franklin | Eurek Alert!
Further information:
http://www.utexas.edu

Further reports about: Energy Texas anticancer apoptosis cancerous chloride death ions sodium synthetic transporters treating

More articles from Life Sciences:

nachricht The birth of a new protein
20.10.2017 | University of Arizona

nachricht Building New Moss Factories
20.10.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

Im Focus: Shrinking the proton again!

Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.

It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

Climate Engineering Conference 2017 Opens in Berlin

10.10.2017 | Event News

 
Latest News

Terahertz spectroscopy goes nano

20.10.2017 | Information Technology

Strange but true: Turning a material upside down can sometimes make it softer

20.10.2017 | Materials Sciences

NRL clarifies valley polarization for electronic and optoelectronic technologies

20.10.2017 | Interdisciplinary Research

VideoLinks
B2B-VideoLinks
More VideoLinks >>>