“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.1004522107About 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 reports about: > Biomedical > Biomedical Science > Degterev > Edition > Medicine > Merit Award > Molecules > Nutrition > PIP3 > PITs > PNAS > Sackler > Science TV > Small Molecule > TUSM > Tufts > Universität Harvard > brain aging > cell death > cell signaling > chemical engineering > signaling pathway
Newly designed molecule binds nitrogen
23.02.2018 | Julius-Maximilians-Universität Würzburg
Atomic Design by Water
23.02.2018 | Max-Planck-Institut für Eisenforschung GmbH
A newly developed laser technology has enabled physicists in the Laboratory for Attosecond Physics (jointly run by LMU Munich and the Max Planck Institute of Quantum Optics) to generate attosecond bursts of high-energy photons of unprecedented intensity. This has made it possible to observe the interaction of multiple photons in a single such pulse with electrons in the inner orbital shell of an atom.
In order to observe the ultrafast electron motion in the inner shells of atoms with short light pulses, the pulses must not only be ultrashort, but very...
A group of researchers led by Andrea Cavalleri at the Max Planck Institute for Structure and Dynamics of Matter (MPSD) in Hamburg has demonstrated a new method enabling precise measurements of the interatomic forces that hold crystalline solids together. The paper Probing the Interatomic Potential of Solids by Strong-Field Nonlinear Phononics, published online in Nature, explains how a terahertz-frequency laser pulse can drive very large deformations of the crystal.
By measuring the highly unusual atomic trajectories under extreme electromagnetic transients, the MPSD group could reconstruct how rigid the atomic bonds are...
Quantum computers may one day solve algorithmic problems which even the biggest supercomputers today can’t manage. But how do you test a quantum computer to...
For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.
In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...
Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale
Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...
15.02.2018 | Event News
13.02.2018 | Event News
12.02.2018 | Event News
23.02.2018 | Physics and Astronomy
23.02.2018 | Health and Medicine
23.02.2018 | Physics and Astronomy