Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Of 50,000 Small Molecules Tested to Fight Cancer, Two Show Promise

03.11.2010
A class of compounds that interferes with cell signaling pathways may provide a new approach to cancer treatment, according to a study published online this week in the Proceedings of the National Academy of Sciences (PNAS) Early Edition. The compounds, called PITs (non-phosphoinositide PIP3 inhibitors), limited tumor growth in mice by inducing cell death.

“PITs cause cells to self-destruct by interfering with the signaling pathways that regulate cell survival. As compounds that promote cell death, PITs show promise in halting the harmful, unwanted growth characteristic of cancer,” said senior author Alexei Degterev, PhD, assistant professor in the biochemistry department at Tufts University School of Medicine (TUSM) and member of the biochemistry program faculty at the Sackler School of Graduate Biomedical Sciences at Tufts.

Degterev teamed up with colleagues at TUSM, Northeastern University, Massachusetts General Hospital, Harvard Medical School, and the National Chemical Laboratory in Pune, India, to identify compounds that could disrupt a cell signaling molecule called PIP3. Out of 50,000 small molecules screened, the team identified two that inhibited PIP3.

“We tested the more stable of these two molecules in mice and found that it inhibited tumor growth and induced cancer cell death,” said co-first author Benchun Miao, PhD, formerly a postdoctoral associate in the biochemistry department at TUSM and fellow in Degterev’s lab and now a postdoctoral associate in the Nutrition and Cancer Laboratory at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University.

“We also found that PITs showed an even stronger anti-tumor effect in cells with high PIP3 levels. In humans, these high-PIP3 cells are responsible for aggressive forms of cancer such as glioblastoma,” said co-first author Igor Skidan, PhD, formerly a postdoctoral fellow in the department of pharmaceutical sciences at Northeastern University and now a senior scientist at Morphotek, Inc.

According to Degterev, PITs are a promising and relatively unexplored approach to cancer treatment. He says that PITs are a new class of compounds that inhibit PIP3, positioned at an early point in a cell signaling pathway over-activated in many human tumors. The study also presents a methodology for identifying other molecules similar to PITs. Degterev hopes that this approach will help researchers isolate other new compounds that halt cancer growth.

“We are not yet at the stage of considering PITS as leads for therapeutics. Our next focus, with our collaborators at National Chemical Laboratory, will be to develop PITS to be more effective,” says Degterev.

This study was supported by the Smith Family Awards for Excellence in Biomedical Research, a National Institute on Aging Mentored Research Scientist Career Development Award, a US Army Innovator Award; as well as the National Cancer Institute and the National Institute on Aging, both parts of the National Institutes of Health. Patent applications related to the discoveries described in this paper have been filed by Tufts University, Harvard University, and the National Chemical Laboratory, India.

Miao B, Skidan I, Yang J, Lugovskoy A, Reibarkh M, Long K, Brazell T, Durugkar KA, Maki J, Ramana CV, Schaffhausen B, Wagner G, Torchilin V, Yuan J, Degterev A. PNAS Early Edition (November 1, 2010). "Small molecule inhibition of phosphatidylinositol-3,4,5-triphosphate (PIP3) binding to pleckstrin homology domains.” Published online November 1, 2010, doi: 10.1073/pnas.1004522107

About Tufts University School of Medicine and the Sackler School of Graduate Biomedical Sciences

Tufts University School of Medicine and the Sackler School of Graduate Biomedical Sciences at Tufts University are international leaders in innovative medical education and advanced research. The School of Medicine and the Sackler School are renowned for excellence in education in general medicine, biomedical sciences, special combined degree programs in business, health management, public health, bioengineering and international relations, as well as basic and clinical research at the cellular and molecular level. Ranked among the top in the nation, the School of Medicine is affiliated with six major teaching hospitals and more than 30 health care facilities. Tufts University School of Medicine and the Sackler School undertake research that is consistently rated among the highest in the nation for its effect on the advancement of medical science.

If you are a member of the media interested in learning more about this topic, or speaking with a faculty member at the Tufts University School of Medicine, the Sackler School of Graduate Biomedical Sciences, or another Tufts health sciences researcher, please contact Siobhan Gallagher at 617-636-6586.

Siobhan Gallagher | Newswise Science News
Further information:
http://www.tufts.edu

More articles from Life Sciences:

nachricht Bolstering fat cells offers potential new leukemia treatment
17.10.2017 | McMaster University

nachricht Ocean atmosphere rife with microbes
17.10.2017 | King Abdullah University of Science & Technology (KAUST)

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

Ocean atmosphere rife with microbes

17.10.2017 | Life Sciences

Neutrons observe vitamin B6-dependent enzyme activity useful for drug development

17.10.2017 | Life Sciences

NASA finds newly formed tropical storm lan over open waters

17.10.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>