Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Smac-ing lung cancer to death

14.11.2007
Howard Hughes Medical Institute researchers have developed a small molecule that can turn the survival signal for a variety of cancer cells into a death signal. The molecule mimics the activity of Smac, a protein that triggers the suicide of some types of cancer cells.

The researchers say their findings suggest that Smac-mimetic compounds could be useful as targeted cancer treatments for lung and other cancers. Such therapy may be less toxic to healthy cells than current compounds used in cancer chemotherapy.

The researchers, led by Howard Hughes Medical Institute investigator Xiaodong Wang, published their findings in the November, 2007, issue of the journal Cancer Cell. Wang is at the University of Texas Southwestern Medical Center.

Cells that are defective or that become unnecessary during growth and development are induced to commit suicide through a finely balanced process known as apoptosis, or programmed cell death. A protein called Smac, which is a shortened version of “second mitochondria-derived activator of apoptosis,” is a part of the cell’s programmed cell death machinery. When that machinery is switched on, Smac is released from the mitochondria and triggers the pathway that kills damaged or abnormal cells. Cancer cells, however, can survive Smac’s death signal by switching off the apoptotic machinery.

... more about:
»Cancer »Smac »apoptosis »death »lung

To see if they could get around this problem, Wang and other researchers have developed small-molecule mimetics of Smac that can enter the cell and trigger apoptosis. These mimetic molecules do their damage without the need for the Smac signal from the mitochondria. In earlier studies, Wang and his colleagues found that a Smac mimetic that they developed in the lab could kill cancer cells in culture. But they found that the cancer cells are only killed when the mimetic molecule is introduced in conjunction with another component of the apoptotic machinery known as TNFá.

In the new studies published in Cancer Cell, Wang and his colleagues found that a significant percentage of human non-small-cell lung cancer cell lines were sensitive to treatment by the Smac mimetic alone. When the researchers introduced those sensitive cells into mice and allowed them to produce tumors, they found that the Smac mimetic caused the tumors to regress and, in some cases, even disappear.

“These findings made us wonder what it was about these cell lines that made them sensitive to the Smac mimetic alone,” said Wang. “Cancer cells are hard to kill, but these cell lines seemed to have already become sensitized to apoptosis.”

The researchers’ studies revealed that the sensitive cell lines produced their own TNFá, so they were already “primed” for apoptosis. The paradox, said Wang, is that TNFá signaling is also part of a complex pathway that gives cancer cells a “survival” signal, offering them a growth advantage. The researchers also found that some breast cancer and melanoma cell lines were sensitive to the Smac mimetic alone.

“Thus, in these cancer cell lines, the TNFá survival advantage turns out to be a fatal flaw, because the same pathway can be switched to apoptosis by Smac mimetics,” said Wang. “So, for some cancers, we might be able to use Smac mimetics as a single treatment agent. And we can use the presence of TNFá as a marker to tell us which tumors will respond to the Smac mimetic alone.”

“People have been suspecting for a long time that some cancer cells may somehow turn on their apoptotic pathway already,” said Wang. “And now we know what pathway they turn on and why. We can take advantage of this phenomenon for potential cancer therapy by switching a signal into a deadly one with Smac mimetics.”

Jennifer Michalowski | EurekAlert!
Further information:
http://www.hhmi.org

Further reports about: Cancer Smac apoptosis death lung

More articles from Life Sciences:

nachricht What happens in the cell nucleus after fertilization
06.12.2016 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Researchers uncover protein-based “cancer signature”
05.12.2016 | Universität Basel

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

Im Focus: Molecules change shape when wet

Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water

In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

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

14.10.2016 | Event News

 
Latest News

Speed data for the brain’s navigation system

06.12.2016 | Health and Medicine

What happens in the cell nucleus after fertilization

06.12.2016 | Life Sciences

IHP presents the fastest silicon-based transistor in the world

05.12.2016 | Power and Electrical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>