Navigation Links
Synthetic compound promotes death of lung-cancer cells, tumors
Date:11/12/2007

DALLAS Nov. 12, 2007 Human lung-cancer tumors grown in mice have been shown to regress or disappear when treated with a synthetic compound that mimics the action of a naturally occurring death-promoting protein found in cells, researchers at UT Southwestern Medical Center report.

The findings, appearing in todays issue of Cancer Cell, suggest that the compound might one day be used in targeted therapies for lung and possibly other cancers, the researchers said.

We found that certain kinds of lung-cancer cells were sensitive to this compound, which sends a signal to cancer cells to self-destruct, said Dr. Xiaodong Wang, professor of biochemistry at UT Southwestern and senior author of the study.

In 2000, Dr. Wang announced the discovery of a cellular protein called Smac, which plays a key role in the normal self-destruction apparatus present in every cell. This process, called apoptosis, is activated when a cell needs to be terminated, such as when a cell is defective or becomes unnecessary during normal growth and development. In cancer cells, the self-destruct mechanism is faulty.

In 2004, Dr. Wang and his colleagues developed a compound that mimics the action of Smac. They found that in cell cultures, the compound killed cancer cells but left healthy cells unaffected. In those studies, however, the Smac mimic only killed cancer cells when it was introduced along with another molecule often involved in the cell-death machinery, called tumor necrosis factor-a, or TNFa.

In the current study, Dr. Wangs research group tested 50 human non-small-cell lung-cancer cell lines in culture and found that 22 percent of them were sensitive to the Smac mimic alone, without having to add TNFa. The researchers also found that the Smac mimic alone was effective against some types of breast cancer and melanoma cells in culture.

The apparent ability of a Smac mimetic, as a single agent, to induce cell death in nearly one-quarter of lung-cancer cell lines tested was quite remarkable, said Dr. Wang, who is a Howard Hughes Medical Institute investigator at UT Southwestern.

The researchers then introduced those sensitive cancer-cell lines into mice, where they grew into tumors. When the lung-tumor-bearing mice were injected with the Smac mimic, the tumors reduced significantly in size, and in some cases, the tumors disappeared completely.

Also tried was a similar experiment treating breast-cancer tumors in mice with the Smac mimic alone. That treatment, however, showed little effect.

The researchers then investigated what made those particular lung-cancer cell lines so sensitive to the Smac mimic alone.

We found that these sensitive cell lines produce their own TNFa, Dr. Wang said.

In addition to aiding in cell death, TNFa also is known, paradoxically, to sometimes play a role in aiding cancer-cell survival and growth. In combination with the Smac mimic, however, the role of this molecule is clear: cell death.

The Smac mimetic is able to exploit certain cancer cells that secrete TNFa and usurp this pro-survival signal to promote cell death, Dr. Wang said.

Not only is single-agent Smac mimetic treatment highly effective at inducing cell death in these cell lines, but it also offers the possibility of highly specific and relatively nontoxic future therapeutic treatments by exploiting certain cancer cells own production of TNFa.

Additional research and tests will be needed before the Smac mimic is tested in humans, Dr. Wang said, adding that detecting the presence of TNFa in a patient could serve as a marker to indicate that the cancer might be sensitive to treatment with the Smac mimic alone.

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 affects cancer cells selectively, it could combat this problem.


'/>"/>

Contact: Amanda Siegfried
amanda.siegfried@utsouthwestern.edu
214-648-3404
UT Southwestern Medical Center  
Source:Eurekalert

Related biology news :

1. Chloroplast f and m Thioredoxins Discovered in Nonphotosynthetic Tissues
2. New microsensor measures volatile organic compounds in water and air on-site
3. Naturally-occurring apple compounds reduce risk of pancreatic cancer
4. Chemical compound present in detergents produce bacteria alterations in agricultural soils
5. Bleeding, not inflammation, is major cause of early lung infection death
6. Small-scale fishing in Mexico rivals industrial fisheries in accidental turtle deaths
7. Scientists find how amber becomes death trap for watery creatures
8. MIT develops tractor beam for cells, more
9. Invasion of the brain tumors
10. Analysis of breast and colon cancer genes finds many areas of differences between tumors
11. Cell response to stress signals predicts tumors in women with common pre-breast cancer
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Synthetic compound promotes death of lung-cancer cells, tumors
(Date:6/22/2016)... , June 22, 2016  The American College of Medical ... Show Executive Magazine as one of the fastest-growing trade ... 25-27 at the Bellagio in Las Vegas ... highest percentage of growth in each of the following categories: ... companies and number of attendees. The 2015 ACMG Annual Meeting ...
(Date:6/21/2016)... 21, 2016 NuData Security announced today that ... of principal product architect and that Jon ... customer development. Both will report directly to ... moves reflect NuData,s strategic growth in its product ... customer demand and customer focus values. ...
(Date:6/15/2016)... York , June 15, 2016 ... new market report titled "Gesture Recognition Market by Application ... Forecast, 2016 - 2024". According to the report, the  ... 11.60 billion in 2015 and is estimated to ... USD 48.56 billion by 2024.  Increasing ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... -- A person commits a crime, and the detective uses ... criminal down. An outbreak of foodborne illness makes ... uses DNA evidence to track down the bacteria that caused ... not. The FDA has increasingly used a complex, cutting-edge technology ... Put as simply as possible, whole genome sequencing is a ...
(Date:6/23/2016)... SAN FRANCISCO , June 23, 2016   ... it has secured $1 million in debt financing from ... to ramp up automation and to advance its drug ... for its new facility. "SVB has been ... goes beyond the services a traditional bank would provide," ...
(Date:6/23/2016)... NEWPORT BEACH, Calif. , June 23, 2016 /PRNewswire/ ... offering new biological discoveries to the medical community, has ... and co-founder Matthew Nunez . "We ... provide us with the capital we need to meet ... funding will essentially provide us the runway to complete ...
(Date:6/23/2016)... ... 2016 , ... Velocity Products, a division of Morris Group, ... exclusively for Okuma CNC machining centers at The International Manufacturing Technology Show, IMTS, ... companies with expertise in toolholding, cutting tools, machining dynamics and distribution, Velocity SMART ...
Breaking Biology Technology: