Ceramide Destroys Breast Tumor Cells

Researchers for the first time have demonstrated that ceramide, a naturally occurring compound that inhibits cell growth, can be administered through the bloodstream to seek and destroy cancer cells in animal models.

"Ceramide is the substance that accumulates in cancer tissues and helps to kill cancer cells when patients undergo chemotherapy and radiation,” said Mark Kester, Ph.D., professor of pharmacology, Penn State College of Medicine, Penn State Milton S. Hershey Medical Center (Hershey, PA, USA). "By boosting the amount of ceramide through an injection in the bloodstream, our study in mice suggests that we can provide a stronger cancer-killing therapy without additional side effects.”

Administering additional ceramide is not a simple task; injected directly in the bloodstream, ceramide is poisonous. However, utilizing nanotechnology methods, Dr. Kester encapsulated the ceramide in tiny bundles called liposomes. "The major problem with ceramide is that it is a lipid and therefore is not soluble in the systemic circulation,” Dr. Kester said. "Packaging ceramide in our nano liposome capsules allows them to travel through the bloodstream without causing toxicity and releases the ceramide in the tumor.”

Even though the process is still not known, ceramide is intrinsically attracted to tumor cells. The liposome-encased ceramide moves through the bloodstream to the tumor where it enters the tumor cells through the tumor's permeable vasculature. The ceramide disrupts the mitochondria, which operate as the energy generators for the cell. This causes apoptosis, or cell death. The ceramide also reduces the vascular network that provides nutrients to the tumors. In this study utilizing lab mice, the ceramide bundles targeted and killed only breast cancer cells, sparing the surrounding normal tissue.

Dr. Kester and coworkers first evaluated the liposomes in a culture of breast cancer cells. By administering ceramide, the number of breast cancer cells decreased by more than 50%. Further cell culture studies demonstrated that ceramide gathered in the mitochondria of the breast cancer cells, lending credence to previous studies that ceramide interferes with the cell structure and causes tumor cell death.

In a breast tumor mouse model, the researchers administered liposome-encased ceramide every other day via intravenous injection. After 21 days, the mice given the liposome-encased ceramide had a six-fold lower tumor volume than the mice treated with "empty” liposomes. The weight of animals treated with ceramide did not differ significantly from the mice treated with empty liposomes, signifying that the ceramide was not toxic (weight would have been lower with toxicity). When the tumors were evaluated, those treated with ceramide demonstrated a 20-fold increase in cellular apoptosis and a 40% decrease in cellular proliferation, compared to the control group.

"Although we've shown that ceramide has an effect on breast tumor cells in mice, breast cancer cells in humans may eventually resist the treatment, suggesting that ceramide should be used in combination with more traditional cancer treatments as a treatment booster," Dr. Kester stated. "Our next step is to explore how additional chemotherapeutic agents could be incorporated into the liposomes for a more lasting effect.”

The study was published in the May 2005 issue of the journal Clinical Cancer.