Featured Research

from universities, journals, and other organizations

Cancer Cell 'Bodyguard' Turned Into Killer

Date:
December 1, 2008
Source:
Oregon State University
Summary:
If you're a cancer cell, you want a protein called Bcl-2 on your side because it decides if you live or die. It's usually a trusted bodyguard, protecting cancer cells from programmed death and allowing them to grow and form tumors. But sometimes it turns into their assassin. Scientists knew it happened, but they didn't know how to actually cause such a betrayal. Now they do and it may lead to the development of new cancer-fighting drugs.

Siva Kolluri, assistant professor of cancer biology in the environmental and molecular toxicology department at OSU.
Credit: Image courtesy of Oregon State University

If you're a cancer cell, you want a protein called Bcl-2 on your side because it decides if you live or die. It's usually a trusted bodyguard, protecting cancer cells from programmed death and allowing them to grow and form tumors. But sometimes it turns into their assassin.

Scientists knew it happened, but they didn't know how to actually cause such a betrayal. Now they do. And it may lead to the development of new cancer-fighting drugs.

Researchers at Oregon State University and the Burnham Institute for Medical Research in La Jolla, Calif., have developed a peptide that converts the Bcl-2 protein from a cancer cell's friend to a foe.

"Now we can force this protein to backstab the cancer cell where it resides," said Siva Kolluri, an assistant professor of cancer biology in the environmental and molecular toxicology department at OSU. He's also the lead author of an article that reported the discovery in the Cancer Cell journal in October.

The key to the conversion is peptide NuBCP-9, a string of nine amino acids that bind to Bcl-2 and attack the mitochondria, the powerhouse of cells. Researchers derived it from Nur77, a nuclear receptor that can cause cells to die. To see if it worked outside the petri dish, researchers injected the peptide and its mirror-image molecule into cancer tumors in mice and found that the cancer cells died and the tumors shrank. To their surprise, they also found that a structurally mirrored-image stable peptide worked as well as the original peptide.

The findings could lead to the development of cancer-fighting drugs that target Bcl-2, Kolluri said. He explained that Bcl-2 is an attractive drug target because its levels are elevated in a majority of human cancers and it is responsible for cancer cells' resistance to many chemotherapeutic drugs and radiation.

Michael Melner, a scientific program director at the American Cancer Society in Atlanta, Ga., said the research Kolluri and his team did "will cause a lot of attention in the cancer field."

"These investigators have done a nice job of combining findings of a basic nature as well as the preliminary studies needed to move to a preclinical evaluation. It's unusual for one single paper to make such a large step forward," he said.

Now one of the next steps, Melner said, is for researchers to determine what types of cancer and what stages of the disease this deadly Bcl-2 converter would combat.

Linda Wolff, a leukemia researcher at the National Institutes of Health's Center for Cancer Research in Bethesda, Md., said the researchers' discovery is "rare" in the world of cancer research. She added that it's important for two reasons.

"First, it may lead to a therapy that could potentially be used against many types of cancer," she said. "The reason for that is because it targets Bcl-2, and Bcl-2 is expressed in many types of cancers. So it could be useful in breast cancer and other carcinomas and leukemia, for example.

"The second reason it's important is that although the peptide they studied causes cancer cells to die, its effect on normal cells seems to be quite minimal," Wolff said. "A big problem in cancer research has been getting therapies that don't kill normal cells."

Dr. David Hockenbery, a member of the Clinical Research Division at the Fred Hutchinson Cancer Research Center in Seattle, Wash., said that this new way of altering a protein so it injures a cell rather than merely disables it "is very unusual." He added that this finding would spur researchers to develop drugs or stable peptides that act on Bcl-2 at the Nur77 binding site.

"Quite conceivably, individual cancers may respond better to one type of Bcl-2 inhibitor than another," he said. "In the future, the availability of several targeting approaches against Bcl-2 should be useful in personalized cancer therapies."

In addition to OSU and the Burnham Institute, the other contributors to the research came from the University of Oklahoma Health Sciences Center and Xiamen University in China. Kolluri started the research project in 2003 when he worked at Burnham.


Story Source:

The above story is based on materials provided by Oregon State University. Note: Materials may be edited for content and length.


Journal Reference:

  1. Kolluri et al. A Short Nur77-Derived Peptide Converts Bcl-2 from a Protector to a Killer. Cancer Cell, 2008; 14 (4): 285 DOI: 10.1016/j.ccr.2008.09.002

Cite This Page:

Oregon State University. "Cancer Cell 'Bodyguard' Turned Into Killer." ScienceDaily. ScienceDaily, 1 December 2008. <www.sciencedaily.com/releases/2008/11/081125113114.htm>.
Oregon State University. (2008, December 1). Cancer Cell 'Bodyguard' Turned Into Killer. ScienceDaily. Retrieved July 29, 2014 from www.sciencedaily.com/releases/2008/11/081125113114.htm
Oregon State University. "Cancer Cell 'Bodyguard' Turned Into Killer." ScienceDaily. www.sciencedaily.com/releases/2008/11/081125113114.htm (accessed July 29, 2014).

Share This




More Health & Medicine News

Tuesday, July 29, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Deadly Ebola Virus Threatens West Africa

Deadly Ebola Virus Threatens West Africa

AP (July 28, 2014) West African nations and international health organizations are working to contain the largest Ebola outbreak in history. It's one of the deadliest diseases known to man, but the CDC says it's unlikely to spread in the U.S. (July 28) Video provided by AP
Powered by NewsLook.com
$15B Deal on Vets' Health Care Reached

$15B Deal on Vets' Health Care Reached

AP (July 28, 2014) A bipartisan deal to improve veterans health care would authorize at least $15 billion in emergency spending to fix a veterans program scandalized by long patient wait times and falsified records. (July 28) Video provided by AP
Powered by NewsLook.com
Two Americans Contract Ebola in Liberia

Two Americans Contract Ebola in Liberia

Reuters - US Online Video (July 28, 2014) Two American aid workers in Liberia test positive for Ebola while working to combat the deadliest outbreak of the virus ever. Linda So reports. Video provided by Reuters
Powered by NewsLook.com
Traditional African Dishes Teach Healthy Eating

Traditional African Dishes Teach Healthy Eating

AP (July 28, 2014) Classes are being offered nationwide to encourage African Americans to learn about cooking fresh foods based on traditional African cuisine. The program is trying to combat obesity, heart disease and other ailments often linked to diet. (July 28) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins