Featured Research

from universities, journals, and other organizations

Fatty acid to enhance anticancer drug

Date:
May 12, 2010
Source:
Helmholtz Association of German Research Centres
Summary:
Scientists in Germany have discovered that bioavailability and efficacy of the blood cancer drug azacytidine increase when the substance is coupled to a fatty acid.

Computer model of the enzyme methyltransferase.
Credit: Frank Lyko, German Cancer Research Center

Scientists of the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) have discovered that bioavailability and efficacy of the blood cancer drug azacytidine increase when the substance is coupled to a fatty acid.

Related Articles


Chemical changes in the genetic material, known as epigenetic modifications, regulate the activity of many genes. Thus, attachment of methyl groups to DNA often inactivates important cellular growth brakes. Therefore, this process called methylation is believed to be a major cause of uncontrolled division of cancer cells. Specific enzymes, the DNA methyltransferases, are responsible for methylation.

Unlike changes in the blueprint of the genetic material, epigenetic mutations are reversible and, thus, cancer cells can be restored to their "normal state." Substances causing this re-programming are already being used as anticancer drugs. Examples are azacytidine and decitabine, which are used in the treatment of a specific type of blood cancer called acute myeloid leukemia. Both substances are incorporated into the cell's genetic material, where they act as a trap for methyltransferases. They form permanent chemical bonds with the enzyme, thereby catching the methyltransferases one by one, so that no more genes are being silenced.

Scientists in Professor Frank Lyko's team at DKFZ were searching for azacytidine variants with enhanced efficacy, because the drug still remains ineffective in many cases even when it is has been established that tumor brakes have been put out of effect by methylation. Researchers believe that this therapy resistance is frequently caused by the fact that not enough of the agent gets into the interior of the cells, because cancer cells lack particular transport molecules in the cell membrane.

The Norwegian company Clavis Pharma produced the azacytidine variants with modified chemical properties. Among the substances studied was CP-4200, a coupled product of azacytidine and a fatty acid (elaidic acid). CP-4200 showed particularly good results. When cancer cells in the culture dish are treated with CP-4200, the amount of methyltransferase molecules in the interior of the cells is reduced. At the same time, the methyl groups bound to the DNA of cancer cells disappear and silenced tumor brakes are reactivated. The investigators assume that the elaidic acid makes it possible even for cells without special transport proteins to take up CP-4200; the substance might reach the cell interior directly through the membrane.

The effectiveness of azacytidine was previously proven only for acute myeloid leukemia. To find out whether CP-4200 shows an increased efficacy range, the investigators compared the two substances in mice suffering from another form of blood cancer, acute lymphatic leukemia. In all treatment tests investigated, the effectiveness of CP-4200 was superior to that of azacytidine. "Coupling to elaidic acid improves the bioavailability of the agent without impeding its epigenetic effect," explains project leader Frank Lyko."Therefore, we see chances of reversing methylation in far more cancer patients in the future and arresting tumor growth in this way."


Story Source:

The above story is based on materials provided by Helmholtz Association of German Research Centres. Note: Materials may be edited for content and length.


Journal Reference:

  1. B. Brueckner, M. Rius, M. R. Markelova, I. Fichtner, P. A. Hals, M. L. Sandvold, F. Lyko. Delivery of 5-Azacytidine to Human Cancer Cells by Elaidic Acid Esterification Increases Therapeutic Drug Efficacy. Molecular Cancer Therapeutics, 2010; DOI: 10.1158/1535-7163.MCT-09-1202

Cite This Page:

Helmholtz Association of German Research Centres. "Fatty acid to enhance anticancer drug." ScienceDaily. ScienceDaily, 12 May 2010. <www.sciencedaily.com/releases/2010/05/100507101851.htm>.
Helmholtz Association of German Research Centres. (2010, May 12). Fatty acid to enhance anticancer drug. ScienceDaily. Retrieved December 19, 2014 from www.sciencedaily.com/releases/2010/05/100507101851.htm
Helmholtz Association of German Research Centres. "Fatty acid to enhance anticancer drug." ScienceDaily. www.sciencedaily.com/releases/2010/05/100507101851.htm (accessed December 19, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Friday, December 19, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Kids Die While Under Protective Services

Kids Die While Under Protective Services

AP (Dec. 18, 2014) As part of a six-month investigation of child maltreatment deaths, the AP found that hundreds of deaths from horrific abuse and neglect could have been prevented. AP's Haven Daley reports. (Dec. 18) Video provided by AP
Powered by NewsLook.com
Dads-To-Be Also Experience Hormone Changes During Pregnancy

Dads-To-Be Also Experience Hormone Changes During Pregnancy

Newsy (Dec. 18, 2014) A study from University of Michigan researchers found that expectant fathers see a decrease in testosterone as the baby's birth draws near. Video provided by Newsy
Powered by NewsLook.com
Prenatal Exposure To Pollution Might Increase Autism Risk

Prenatal Exposure To Pollution Might Increase Autism Risk

Newsy (Dec. 18, 2014) Harvard researchers found children whose mothers were exposed to high pollution levels in the third trimester were twice as likely to develop autism. Video provided by Newsy
Powered by NewsLook.com
UN: Up to One Million Facing Hunger in Ebola-Hit Countries

UN: Up to One Million Facing Hunger in Ebola-Hit Countries

AFP (Dec. 17, 2014) Border closures, quarantines and crop losses in West African nations battling the Ebola virus could lead to as many as one million people going hungry, UN food agencies said on Wednesday. Duration: 00:52 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