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.

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 July 23, 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 July 23, 2014).

Share This




More Health & Medicine News

Wednesday, July 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Courts Conflicted Over Healthcare Law

Courts Conflicted Over Healthcare Law

AP (July 22, 2014) Two federal appeals courts issued conflicting rulings Tuesday on the legality of the federally-run healthcare exchange that operates in 36 states. (July 22) Video provided by AP
Powered by NewsLook.com
Why Do People Believe We Only Use 10 Percent Of Our Brains?

Why Do People Believe We Only Use 10 Percent Of Our Brains?

Newsy (July 22, 2014) The new sci-fi thriller "Lucy" is making people question whether we really use all our brainpower. But, as scientists have insisted for years, we do. Video provided by Newsy
Powered by NewsLook.com
Scientists Find New Way To Make Human Platelets

Scientists Find New Way To Make Human Platelets

Newsy (July 22, 2014) Boston scientists have discovered a new way to create fully functioning human platelets using a bioreactor and human stem cells. Video provided by Newsy
Powered by NewsLook.com
Gilead's $1000-a-Pill Drug Could Cure Hep C in HIV-Positive People

Gilead's $1000-a-Pill Drug Could Cure Hep C in HIV-Positive People

TheStreet (July 21, 2014) New research shows Gilead Science's drug Sovaldi helps in curing hepatitis C in those who suffer from HIV. In a medical study, the combination of Gilead's Hep C drug with anti-viral drug Ribavirin cured 76% of HIV-positive patients suffering from the most common hepatitis C strain. Hepatitis C and related complications have been a top cause of death in HIV-positive patients. Typical medication used to treat the disease, including interferon proteins, tended to react badly with HIV drugs. However, Sovaldi's %1,000-a-pill price tag could limit the number of patients able to access the treatment. TheStreet's Keris Lahiff reports from New York. Video provided by TheStreet
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