GAINESVILLE, Fla. -- University of Florida researchers have taken the first step in making a frequently used anti-cancer drug safe for long-term use.
Doxorubicin, often used to kill tumor cells, also destroys heart cells and can therefore be used on a patient only for a short period of time. UF researchers Pattie Green and Christiaan Leeuwenburgh are looking for a way to protect heart cells, allowing doxorubicin to be used longer, until all cancer cells are dead.
If successful, their study could pave the way for drug therapy that could effectively treat many types of cancer.
"It's likely there's a way to design a pathway to kill tumor cells but not heart cells," said Green, a postdoctoral fellow working with UF's College of Health and Human Performance.
The study will be presented in April at the Conference of Experimental Biology.
Green and Leeuwenburgh, an assistant professor in UF's department of exercise and sport sciences, studied cultures of heart cells treated with doxorubicin to determine how the cells begin to die through a process called apoptosis.
"In apoptosis, the environment around the cell becomes unfriendly and the cell initiates a program that results in its own death," Green said. Doxorubicin creates this "unfriendly" environment, and caspases -- a class of enzymes that are activated when a cell undergoes apoptosis -- begin to break up the cell.
Green and Leeuwenburgh looked specifically at these caspases to determine how they triggered cell death. There are nine different caspases, only some of which are activated each time a cell begins to die.
Caspase-3 is activated to trigger heart cell death, while researchers suspect that a different caspase is activated to trigger cancer cell death. Because the caspases differ, researchers say there may be a way to hinder caspase activation in heart cells while protecting the activation abilities of caspases in cancer cells. That would prevent cell death in the heart while promoting cell death in the cancerous tumor.
"It would be possible to design drugs to inhibit the activation of some caspases but not others," Green said.
Green said the answer may be as simple as giving patients regulated doses of anti-oxidants, such as vitamins E and C. Preliminary research at UF shows promising results, she said.
"We're trying to look at whether anti-oxidants can protect against this cell damage in the heart," Green said. "It's possible that we can optimize a dose of anti-oxidants to be given concurrent with the drug that may specifically inhibit the caspases."
If the toxic effects of doxorubicin can be prevented with simple treatments, cancer patients likely will have a higher chance of survival and fewer side effects during treatment.
"This could have tremendous implications," Leeuwenburgh said. "It needs to become clear that it is beneficial to take anti-oxidants with doxorubicin, but the data isn't all there yet. By this summer, we'll have some more information about the effects."