Iron key to brain tumor drug delivery

June 2, 2011, Pennsylvania State University

Brain cancer therapy may be more effective if the expression of an iron-storing protein is decreased to enhance the action of therapeutic drugs on brain cancer cells, according to Penn State College of Medicine researchers.

Malignant glioblastoma multiforme is a deadly brain tumor for which no long-term effective cure exists. Because drugs in the blood do not pass from the blood vessels to the brain, effective amounts of do not reach the tumor. Increasing dosages damage normal brain tissue and cause significant neurological damage. These dosages also would likely be harmful to other organs in the body. However, by increasing the sensitivity of the cancer cells to drugs, the effectiveness of treatment can be increased.

"About half of all are resistant to chemotherapy and new therapeutic strategies are urgently needed to treat this cancer," said James Connor, Ph.D., Distinguished Professor and vice-chairman of neurosurgery.

Connor and his graduate student Xiaoli Liu took advantage of the high iron requirements of the cells to target ferritin, a protein that stores iron in all cells.

"High levels of iron are required in cancer cells to meet the energy requirements associated with their rapid growth," Connor said. "In addition, iron is essential for general cell health."

Working with Achuthamangalam Madhankumar, Ph.D., assistant professor of neurosurgery, the researchers used liposomes -- tiny lipid containers -- to deliver a fragment of RNA called interference or siRNA, to . The siRNA targets the molecular machinery of the cell so that the protein cannot be made -- a process known as downregulation. By targeting and turning off ferritin in , the protective function of H-ferritin disappears and the sensitivity to chemotherapy increases.

Using ferritin siRNA, the decreases by 80 percent within 48 hours providing a window of opportunity for enhanced sensitivity to the chemotherapeutic agent. The researchers studied whether silencing ferritin would lower the effective dosage of BCNU, a chemotherapy drug used in brain tumor treatment and one of the few approved for brain cancer. While BCNU is effective, it has serious side effects limiting its use.

The use of siRNA reduces the amount of BCNU needed for tumor suppression by more than half in mice, according to the researchers, who published their findings in the journal Cancer Research.

"Our results further indicate that a nanoliposomal delivery mechanism can increase the efficacy of siRNA and optimize the amount of siRNA delivered," Connor said. "By silencing the ferritin gene, tumor sensitivity to chemotoxins was increased. The results from this project are a promising initial step toward the development of siRNA gene therapy involving ferritin for the treatment of multiple tumor types."

Related Stories

Recommended for you

Single blood test screens for eight cancer types

January 18, 2018
Johns Hopkins Kimmel Cancer Center researchers developed a single blood test that screens for eight common cancer types and helps identify the location of the cancer.

Researchers find a way to 'starve' cancer

January 18, 2018
Researchers at Vanderbilt University Medical Center (VUMC) have demonstrated for the first time that it is possible to starve a tumor and stop its growth with a newly discovered small compound that blocks uptake of the vital ...

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.

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.