Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Chemical switch determines if healthy cells are killed by chemotherapy

04.10.2002


Investigators at Washington University School of Medicine in St. Louis have discovered a mechanism that helps explain why healthy cells are not killed by DNA-damaging cancer chemotherapy drugs. The findings are published in the Oct. 4 issue of the journal Cell.



DNA-damaging agents are the most common kind of drugs used to treat cancer. Like most chemotherapy drugs, these are carried in the blood and travel throughout the body. They work by irreparably gumming up DNA in rapidly dividing tumor cells. That damage then triggers the cells to self-destruct through a natural process known as apoptosis, or active cell death.

The drugs also can harm rapidly dividing healthy cells, such as those in the hair follicles, but most healthy cells are unaffected. It is not known why these drugs do not trigger apoptosis in healthy cells.


"The standard answer is that tumor cells are dividing and normal cells are not," says Steve J. Weintraub, M.D., assistant professor of surgery, division of urologic surgery, of medicine and of cell biology and physiology. "But that’s an observation, not an explanation."

The study led by Weintraub found that healthy, nondividing cells have a biochemical switch that when triggered allows apoptosis. The switch is found in a protein that blocks apoptosis known as Bcl-xL.

"Our findings show that if Bcl-xL is inactivated through a chemical process known as deamidation, DNA-damaging chemotherapy will kill even healthy cells," says Weintraub, who is a researcher with the Cellular Proliferation research program at the Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine.

The study focuses on a family of proteins known as Bcl-2, which play a central role in both promoting and inhibiting apoptosis. The investigators first exposed cancer cells from bone, ovarian and other tumors to the anti-cancer drug cisplatin. When they looked at the Bcl-2 proteins from the cells that had died by apoptosis, they found that in each case one member of the Bcl-2 family, the protein Bcl-xL, had been modified by deamidation.

Deamidation makes slight changes in two amino acids in the Bcl-xL protein. As if someone had thrown a switch, those changes alter the shape of Bcl-xL and thereby inactivate it. In its active state, Bcl-xL is tightly joined with another Bcl-2 protein that when free triggers apoptosis. When Bcl-xL is switched off through deamidation, it releases the second protein, and apoptosis can proceed.

The researchers also exposed a line of healthy, nondividing human fibroblasts and several lines of mouse fibroblasts to cisplatin. In some of the cells, the investigators had artificially inactivated the Bcl-xL protein. They found that cells with normal Bcl-xL were not affected by the drug, while those with the inactive Bcl-xL protein died by apoptosis, indicating they were now susceptible to cisplatin.

"Our findings show that normal cells somehow suppress the signal that throws the switch and avoid self-destructing," says Weintraub. They also suggest that tumor cells that suppress the same signal also might be resistant to chemotherapy drugs, he says.

Weintraub is now studying the nature and regulation of the signal that targets Bcl-xL.

Darrell E. Ward | EurekAlert!
Further information:
http://medinfo.wustl.edu/

More articles from Health and Medicine:

nachricht Organ-on-a-chip mimics heart's biomechanical properties
23.02.2017 | Vanderbilt University

nachricht Researchers identify cause of hereditary skeletal muscle disorder
22.02.2017 | Klinikum der Universität München

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

From rocks in Colorado, evidence of a 'chaotic solar system'

23.02.2017 | Physics and Astronomy

'Quartz' crystals at the Earth's core power its magnetic field

23.02.2017 | Earth Sciences

Antimicrobial substances identified in Komodo dragon blood

23.02.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>