Scientists find Achilles' heel of cancer cells

November 5, 2012, Helmholtz Association of German Research Centres

Several substances inhibiting so-called HDAC enzymes have been studied in trials searching for new anti-cancer drugs in recent years. "Trials have shown that HDAC inhibitors are very effective in arresting growth of cultured cancer cells. But apart from a very rare type of lymphoma, these drugs unfortunately do not clinically affect malignant tumors," says Prof. Dr. Olaf Witt, who heads a research department at DKFZ and is pediatrician at the Center for Child and Adolescent Medicine of Heidelberg University Hospital.

In the cell, histone deacetylases (HDAC) are responsible for removing small chemical tags called acetyl groups from . Histones serve as coils the genetic material wraps around in the nucleus. The presence or absence of acetyl tags determines where genetic material is accessible and can get transcribed.

Now this is where Witt and his colleagues suspect the reason for the problems in of HDAC inhibitors. Currently available substances equally block all members of the large family of HDAC enzymes. Thus, they interfere with vital and also harm healthy cells. This can lead to severe side effects preventing their administration at a sufficient dosage.

Searching for a solution to this dilemma, Witt's team came across a member of the HDAC family, HDAC11, which was identified only recently. The researchers could show that many , including cells of breast, liver and renal cancers, produce extraordinary high levels of HDAC11. This has not been observed in healthy cells, and hardly any specific functions of HDAC11 are known there. "It therefore seemed obvious that a specific HDAC11 inhibitor would specifically target tumor cells, where this enzyme appears to play a critical role," says Dr. Hedwig Deubzer, first author of the article.

As there are no specific HDAC11 inhibitors available yet, the team took a different approach to verify their hypothesis. Using molecular techniques, they turned off production of HDAC11 in breast, colon, prostate and ovarian cancer cell lines and likewise in control cells of healthy tissues. The result: Cancer cells without HDAC11 were impaired in viability and more often underwent cell death (apoptosis). By contrast, loss of HDAC11 did not cause any noticeable changes in normal cells.

"The result suggests that selective blocking of HDAC11 would act exclusively on ," says Hedwig Deubzer. Numerous highly specific inhibitors against various cancer-relevant enzymes have been developed in recent years, with some of them already approved as drugs. This encourages the Heidelberg research team, jointly with Bayer Healthcare, to look for a suitable substance that specifically targets HDAC11.

HDAC inhibitors belong to a group of drugs classified by researchers as "epigenetically effective" drugs. These agents influence the chemical tags that a cell attaches directly to the genetic material or to the packaging proteins of genetic material such as histones. These tags play a substantial role in regulating gene activity. In the past few years, evidence has been accumulating that epigenetic tagging defects promote cancer development. Novel agents such as HDAC inhibitors are intended to correct such defects.

Explore further: Blocking DNA: HDAC inhibitor targets triple negative breast cancer

More information: Hedwig E. Deubzer, Marie C. Schier, Ina Oehme, Marco Lodrini, Bernard Haendler, Anette Sommer and Olaf Witt: HDAC11 is a novel drug target in carcinomas. International Journal of Cancer 2012, DOI:10.1002/ijc.27876

Related Stories

Blocking DNA: HDAC inhibitor targets triple negative breast cancer

May 21, 2012
The histone de-acetylase (HDAC) inhibitor panobinostat is able to target and destroy triple negative breast cancer, reveals a new study published in BioMed Central's open access journal Breast Cancer Research. Researchers ...

Drug may slow spread of deadly eye cancer

November 28, 2011
A drug commonly used to treat seizures appears to make eye tumors less likely to grow if they spread to other parts of the body, according to researchers at Washington University School of Medicine in St. Louis.

Drug shows promise for triple-negative breast cancer

July 3, 2012
(Medical Xpress) -- A promising new therapy for hard-to-treat triple-negative breast cancer has been reported in the journal Breast Cancer Research by a team at the Tulane University School of Medicine, led by Dr. Bridgette ...

Recommended for you

How cancer metastasis happens: Researchers reveal a key mechanism

January 18, 2018
Cancer metastasis, the migration of cells from a primary tumor to form distant tumors in the body, can be triggered by a chronic leakage of DNA within tumor cells, according to a team led by Weill Cornell Medicine and Memorial ...

Modular gene enhancer promotes leukemia and regulates effectiveness of chemotherapy

January 18, 2018
Every day, billions of new blood cells are generated in the bone marrow. The gene Myc is known to play an important role in this process, and is also known to play a role in cancer. Scientists from the German Cancer Research ...

These foods may up your odds for colon cancer

January 18, 2018
(HealthDay)—Chowing down on red meat, white bread and sugar-laden drinks might increase your long-term risk of colon cancer, a new study suggests.

The pill lowers ovarian cancer risk, even for smokers

January 18, 2018
(HealthDay)—It's known that use of the birth control pill is tied to lower odds for ovarian cancer, but new research shows the benefit extends to smokers or women who are obese.

Researchers develop swallowable test to detect pre-cancerous Barrett's esophagus

January 17, 2018
Investigators at Case Western Reserve University School of Medicine and University Hospitals Cleveland Medical Center have developed a simple, swallowable test for early detection of Barrett's esophagus that offers promise ...

Scientists zoom in to watch DNA code being read

January 17, 2018
Scientists have unveiled incredible images of how the DNA code is read and interpreted—revealing new detail about one of the fundamental processes of life.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.