A Penn State College of Medicine study shows for the first time in an animal
model that ceramide, a naturally occurring substance that prevents the growth
of cells, can be administered through the blood stream to target and kill
"Ceramide is the substance that accumulates
in cancer tissues and helps to kill cancer cells
when patients undergo chemotherapy and radiation," said
Mark Kester, professor of pharmacology, Penn State
College of Medicine, Penn State Milton S. Hershey
Medical Center. "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."
This study, titled "Systemic Delivery of Liposomal
Short-Chain Ceramide Limits Solid Tumor Growth in
Murine Models of Breast Adenocarcinoma," was
published in the May issue of Clinical Cancer Research,
a journal of the American Association for Cancer
Administering extra ceramide is not as easy as it
seems. Injected directly into the bloodstream, ceramide
is toxic. But Kester applied knowledge gained from
previous laboratory studies in nanotechnology and
encapsulated the ceramide in tiny bundles called
"The major problem with ceramide is that it
is a lipid and therefore is not soluble in the systemic
circulation," Kester said. "Packaging ceramide
in our nano liposome capsules allows them to travel
through the bloodstream without causing toxicity
and release the ceramide in the tumor."
Although the mechanism remains unknown, ceramide
is inherently attracted to tumor cells. The liposome-encased
ceramide travels through the bloodstream to the tumor
where it enters the tumor cells through the tumor's
leaky vasculature. The ceramide disrupts the mitochondria,
which act as the energy producer for the cell. This
causes apoptosis, or cell death. The ceramide also
reduces the vascular network that feeds the tumor.
In this study in mice, the ceramide bundles targeted
and destroyed only breast cancer cells, sparing the
surrounding healthy tissue.
Kester and his team first tested the ceramide-filled
liposomes in a culture of breast cancer cells. The
administration of ceramide reduced by more than 50
percent the number of breast cancer cells.
Additional cell culture studies showed that ceramide
accumulated in the mitochondria of the breast cancer
cells supporting earlier laboratory studies that
ceramide interferes with the structure of the cell
and causes tumor death.
In a mouse model of breast tumors, the team administered
liposome-encased ceramide every other day via intravenous
After 21 days, the mice treated with the liposome-encased
ceramide had a six-fold lower tumor volume than the
mice treated with "empty"
The weight of animals treated with ceramide did
not vary 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 examined, those treated with
ceramide showed a 20-fold increase in cellular apoptosis
and a 40 percent decrease in cellular proliferation,
or growth, 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
Kester said. "Our next step is to explore how
additional chemotherapeutic agents could be incorporated
into the liposomes for a more lasting effect."
Other study team members were: Thomas C. Stover,
Ph.D., Arati Sharma, Ph.D., Department of Pharmacology,
and Gavin P. Robertson, Ph.D., Departments of Pharmacology,
Pathology, and Dermatology, Penn State College of
Medicine, Penn State Milton S. Hershey Medical Center.
All research methods were approved by the Animal
Care and Use Committee of Penn State College of Medicine.
This study was supported by a grant from the National
Institutes of Health.
Contact: Amy Buehler Stranges firstname.lastname@example.org