Featured Research

from universities, journals, and other organizations

Researchers Develop New Method For Fighting Leukemia

Date:
January 16, 2007
Source:
Virginia Commonwealth University
Summary:
Researchers at Virginia Commonwealth University's Massey Cancer Center have created a new method to improve the antileukemic activity of a novel agent that triggers programmed cell death, a development that could lead to more effective strategies for fighting leukemia and other malignancies.

Researchers at Virginia Commonwealth University's Massey Cancer Center have created a new method to improve the antileukemic activity of a novel agent that triggers programmed cell death, a development that could lead to more effective strategies for fighting leukemia and other malignancies.

Related Articles


The cell death process, or apoptosis, is characteristically impaired in cancer cells. The process is regulated by a large family of proteins that either promotes or inhibits cell death. Recently, considerable attention has focused on the development of agents that inhibit the actions of antiapoptotic members of this family.

One such agent, known as ABT-737, potently blocks the pro-survival effects of two proteins, Bcl-2 and Bcl-xL, according to Steven Grant, M.D., Massey's associate director for translational research and co-leader of the cancer center's cancer cell biology program. Grant is senior author of the study, which is published in the Jan. 15 issue of the journal Cancer Research.

In laboratory experiments, ABT-737 has been shown to be very effective in killing tumor cells. However, this agent is unable to block the actions of another anti-apoptotic family member, Mcl-1, and it has been found that increased expression of Mcl-1 in tumor cells significantly reduces the anti-tumor effectiveness of ABT-737.

Grant and colleagues demonstrated that interventions that reduce levels of Mcl-1 in leukemia cells dramatically increase the effectiveness of ABT-737. Specifically, they employed an agent called roscovitine to block the synthesis of Mcl-1 at the RNA level. Grant said that because Mcl-1 is a very short-lived protein, disrupting its synthesis rapidly lowers Mcl-1 levels.

Grant's team found that the simultaneous reduction in Mcl-1 expression in conjunction with disruption of the anti-apoptotic actions of Bcl-2 and Bcl-xL by ABT-737 resulted in the marked activation of an important pro-apoptotic protein known as Bak. Grant said that when Bak is freed from its constraints by these actions, it cooperates with other pro-death proteins to induce mitochondrial damage, culminating in the dramatic onset of apoptosis.

"Our findings are significant because we were able to employ pharmacologic agents to recapitulate the death process that occurs in normal cells, and which is impaired in their neoplastic counterparts," said Grant. "These findings could also have significant translational implications for the treatment of leukemia and potentially other malignancies."

"For example, analogs of roscovitine have recently entered the clinic, and a number of other agents capable of reducing Mcl-1 levels in tumor cells are currently being developed," he said.

Based upon the findings of Grant's group, regimens combining such agents with Bcl-2 antagonists like ABT-737 could represent a particularly effective treatment strategy in leukemia and various other malignancies.

This work was supported by grants from the National Institutes of Health, the Leukemia and Lymphoma Society of America, and the Department of Defense.

Grant, a professor of medicine and the Shirley Carter and Sture Gordon Olsson Professor of oncology, worked with a team that included: Shuang Chen, Ph.D., Yun Dai, Ph.D., and Hisashi Harada, M.D., Ph.D., all in the VCU Department of Medicine; and Paul Dent, Ph.D., a professor in the VCU Department of Biochemistry.


Story Source:

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


Cite This Page:

Virginia Commonwealth University. "Researchers Develop New Method For Fighting Leukemia." ScienceDaily. ScienceDaily, 16 January 2007. <www.sciencedaily.com/releases/2007/01/070116130950.htm>.
Virginia Commonwealth University. (2007, January 16). Researchers Develop New Method For Fighting Leukemia. ScienceDaily. Retrieved October 31, 2014 from www.sciencedaily.com/releases/2007/01/070116130950.htm
Virginia Commonwealth University. "Researchers Develop New Method For Fighting Leukemia." ScienceDaily. www.sciencedaily.com/releases/2007/01/070116130950.htm (accessed October 31, 2014).

Share This



More Health & Medicine News

Friday, October 31, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Fauci Says Ebola Risk in US "essentially Zero"

Fauci Says Ebola Risk in US "essentially Zero"

AP (Oct. 30, 2014) NIAID Director Anthony Fauci said the risk of Ebola becoming an epidemic in the U.S. is essentially zero Thursday at the Washington Ideas Forum. He also said an Ebola vaccine will be tested in West Africa in the next few months. (Oct. 30) Video provided by AP
Powered by NewsLook.com
Nurse Defies Ebola Quarantine With Bike Ride

Nurse Defies Ebola Quarantine With Bike Ride

AP (Oct. 30, 2014) A nurse who vowed to defy Maine's voluntary quarantine for health care workers who treated Ebola patients followed through on her promise Thursday, leaving her home for an hour-long bike ride. (Oct. 30) Video provided by AP
Powered by NewsLook.com
Pot-Infused Edibles Raise Concerns in Colorado

Pot-Infused Edibles Raise Concerns in Colorado

AFP (Oct. 30, 2014) Colorado may have legalized marijuana for recreational use, but the debate around the decision still continues, with a recent - failed - attempt to ban cannabis-infused edibles. Duration: 01:53 Video provided by AFP
Powered by NewsLook.com
British Navy Ship Arrives in Sierra Leone With Ebola Aid

British Navy Ship Arrives in Sierra Leone With Ebola Aid

AFP (Oct. 30, 2014) The British ship RFA ARGUS arrived in Sierra Leone to deliver supplies and equipment to help the fight against Ebola. Duration: 00:42 Video provided by AFP
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:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

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