Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Small, Smac-like molecule encourages death of cancer cells


Researchers at UT Southwestern Medical Center at Dallas have developed a small molecule that mimics the action of a key "death-promoting" protein in cells, a finding that could lead to more effective cancer therapies with fewer side effects.
In the Sept. 3 issue of the journal Science, the researchers report on this new compound and how it behaves like the cellular protein Smac, a molecule that lifts barriers to cell death. Dr. Xiaodong Wang, professor of biochemistry and one of the authors of the Science paper, discovered Smac in 2000. "Every cell in our body has a self-destruction apparatus that becomes activated when a cell needs to be terminated," Dr. Wang said. "The Smac protein is one component of this normal cell-suicide process, called apoptosis."

Apoptosis, for example, is required for the removal of webbing between the toes and fingers of a developing fetus, as well as for the elimination of surplus neurons during the development of the human brain.

In healthy cells, Smac is sequestered within cell compartments called mitochondria, where the protein resides until mitochondria receive signals to release it. Smac then interacts with other molecules called inhibitor-of-apoptosis proteins (IAPs), which, if not countered by Smac, will keep the cell alive and growing.

In cancer cells, IAPs tend to be overexpressed, and the signals that tell mitochondria to release Smac are often defective. That’s why the UT Southwestern-developed Smac mimic, which can enter the cytoplasm of cells unhindered, is an important step in developing new cancer therapies, said Dr. Patrick Harran, associate professor of biochemistry and an author of the study.

The compound, which so far has only been tested on cells in culture, does not appear to harm normal cells, just cancer cells, said Dr. Wang, who is a Howard Hughes Medical Institute investigator and holds the George L. MacGregor Distinguished Chair in Biomedical Science at UT Southwestern. He said other research groups as well as pharmaceutical companies have been trying to develop a small- molecule Smac mimic.

The challenge for cancer therapies now is that they also tend to kill normally growing cells as well as cancer cells, which results in undesirable side effects," he said. "Because this compound appears to impact cancer cells selectively, it could combat this problem."

The Smac mimic was actually discovered by accident. Based on information about how Smac binds to IAPs, the researchers designed molecules they thought would mimic this interaction. They prepared and screened hundreds of candidates. Smac is a large molecule and is also a dimer, which means that is it made up of two identical halves. Dr. Harran, an organic chemist, said their original candidate molecules were monomers, able to imitate just one half of the two-headed protein. "While working with a particular monomer, we performed a chemical reaction that caused it to dimerize," Dr. Harran said. "Even though we didn’t realize this had happened at first, the dimer’s activity as a Smac mimic was off the charts relative to everything else in our collection."

The monomer also showed activity, but it was not nearly as effective at facilitating cell death as the dimer. One of the advantages of the Smac mimic, Dr. Wang said, is that if cancer treatments were to be developed from it, dosages would likely be small. "There is reason to believe that this could be one of the first examples of a catalytic drug," Dr. Harran said. "You may not need one Smac-mimic molecule for each IAP in a cell. You likely need fewer of our Smac mimics than IAPs to neutralize IAP effects, because once the cell death program gets started, it generates more Smac-like activity as it proceeds." Dr. Wang said, "If this turns out to be true, it’s remarkable, because then you would only need a tiny amount to have a dramatic impact."

The next step in the research is to test the compound in animals. "If it does well, hopefully it will someday find its way to people," he said. "That’s the ultimate goal."

Amanda Siegfried | EurekAlert!
Further information:

More articles from Life Sciences:

nachricht First time-lapse footage of cell activity during limb regeneration
25.10.2016 | eLife

nachricht Phenotype at the push of a button
25.10.2016 | Institut für Pflanzenbiochemie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Etching Microstructures with Lasers

Ultrafast lasers have introduced new possibilities in engraving ultrafine structures, and scientists are now also investigating how to use them to etch microstructures into thin glass. There are possible applications in analytics (lab on a chip) and especially in electronics and the consumer sector, where great interest has been shown.

This new method was born of a surprising phenomenon: irradiating glass in a particular way with an ultrafast laser has the effect of making the glass up to a...

Im Focus: Light-driven atomic rotations excite magnetic waves

Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion

Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Ice shelf vibrations cause unusual waves in Antarctic atmosphere

25.10.2016 | Earth Sciences

Fluorescent holography: Upending the world of biological imaging

25.10.2016 | Power and Electrical Engineering

Etching Microstructures with Lasers

25.10.2016 | Process Engineering

More VideoLinks >>>