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 Millions through license revenues
27.04.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn

nachricht New High-Performance Center Translational Medical Engineering
26.04.2017 | Fraunhofer ITEM

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: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Fighting drug resistant tuberculosis – InfectoGnostics meets MYCO-NET² partners in Peru

28.04.2017 | Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

 
Latest News

Wireless power can drive tiny electronic devices in the GI tract

28.04.2017 | Medical Engineering

Ice cave in Transylvania yields window into region's past

28.04.2017 | Earth Sciences

Nose2Brain – Better Therapy for Multiple Sclerosis

28.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>