Fatty acid to enhance anticancer drug--pieces of the puzzle

Some things to think about:

ScienceDaily (May 12, 2010) — 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 reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by Helmholtz Association of German Research Centres, via EurekAlert!, a service of AAAS.

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


  • soromer
    soromer Member Posts: 130
    I especially like this passage:

    "Unlike changes in the blueprint of the genetic material, epigenetic mutations are reversible and, thus, cancer cells can be restored to their "normal state."

    Epigenetic mutations are reversible, huh? Honestly, that is not something that I understood before. No wonder there's so much effort to figure out ways--via allopathy or other healing paradigms--to get the cancer cells to play nicely with others again.

    Thanks for your diligence and also for sharing the fruits of your research, Claudia.

  • california_artist
    california_artist Member Posts: 816 Member
    I just get so excited when somebody gets it, and is interested.
    So, briefly. If you think of epigenetics as the puppeteer and your genes as the puppets, you will understand the relationship between the two. The science of epigenetics is the science of how you, by your actions, can turn your genes-off-or on. It is the bomb!

    So, i typed epigenetics pbs in the google search engine and a lot of things come up. Ghost in the Genes addresses more ancestral things but the one about the twins is very relevant.

    It is all about your actions.
    And there is a book that originally got me turned onto all this called Survival of the Sickest, fascinating.

    There is absolutely hope out there. That is why I feel so strongly that we don't have to die from this disease. We can choose to change our actions along with modern medicines wares if that's what you also choose. Best to you and yours.

    The youTube one is very interesting.

    www.youtube.com/watch?v=YVwhJXqIG9cSep 14, 2007 - 3 min - Uploaded by PBSAdd to. NOVA | Hunting the Hidden Dimension | PBSby PBS29247 views ... The Epigenetics of Identical Twinsby ...

    1. NOVA | Epigenetics - PBS
    Jul 1, 2007 – Environmental factors can alter the way our genes are expressed, making even identical twins different.
    1. NOVA | Epigenetic Therapy - PBS
    Oct 16, 2007 – Dr. Jean-Pierre Issa examines the connection between ...
    1. NOVA | Ghost in Your Genes | PBS
    Epigenetic Therapy Dr. Jean-Pierre Issa examines the connection between ...