A drug commonly used to treat the symptoms of arthritis in humans is showing promise in reducing both the number and the size of cancerous breast tumors in animals.
A new study in rats examined the effectiveness of the drug celecoxib (brand name Celebrex) in fighting breast cancer. When compared with a control group, rats who were fed celecoxib had a 68 percent decrease in tumor incidence and an 81 percent decrease in average tumor size.
While the drug's anti-tumor effects have yet to be tested in humans in a clinical trial, researchers at Ohio State University say celecoxib shows great promise as a tool that someday may help treat and even prevent breast cancer. Celecoxib belongs to the family of nonsteroidal anti-inflammatory drugs (NSAIDs), which include the pain-reducers aspirin and ibuprofen.
The research appears in a recent issue of the journal Cancer Research.
"Across the board, regular intake of NSAIDs lowers the risk of breast cancer," said Randall Harris, co-author of the study and a professor of epidemiology at Ohio State. "NSAIDs inhibit an enzyme that is produced by a gene that is normally silent in breast tissue. Too much of this enzyme in breast tissue leads to the initiation and promotion of breast cancer."
The culprit enzyme, cyclooxygenase-2 (COX-2), is normally triggered only during the body's response to foreign invaders, such as viruses and bacteria. But for reasons unknown to researchers, there is a proliferation of COX-2 in the breast tissue of patients with breast cancer, Harris said. This abundance causes a "prostaglandin cascade" - a flow of biochemicals that fights invaders. Prostaglandins are hormone-like compounds in the body that initiate the body's immune response.
NSAIDs turn off the prostaglandin cascade, Harris said. "There is something about COX-2 and the ensuing cascade that encourages carcinogenesis, and celecoxib seems to turn it around."
Harris and his colleagues separated 120 female rats into three treatment groups. Forty received 1,500 mg of celecoxib for every kilogram of food in their diet; 40 received an equivalent amount of ibuprofen per kilogram of their diet; and 40 served as the control group, receiving only a powdered diet. The drug dosages given to rats in this study were comparable to the average daily therapeutic dose of either drug for a human - about 100 to 200 mg.
After seven days on the respective diets, each rat was injected with DMBA, a carcinogen which causes breast tumors. The diets were continued for 105 more days.
At 28 days after the DMBA injection, the researchers examined the rats for tumors. "It takes at least four to five weeks for the tumors to become large enough to detect by palpation," Harris said. At the end of the experiment, all animals were sacrificed and the tumors extracted and measured.
The researchers found that 13 of the 40 rats given celecoxib had developed malignant tumors, while 24 of the 40 rats in the ibuprofen group developed cancerous tumors. Each of the 40 rats in the control group had developed malignant tumors; many animals in this group had also developed multiple tumors.
Researchers detected the majority of tumors in the celecoxib group much later than they did in the control group (95 vs. 58 days). In the ibuprofen group, most of the tumors were detected at 86 or more days after DMBA injection.
Harris also noted that the rats that had received celecoxib experienced no toxic side effects sometimes associated with NSAIDs, such as weight loss, ulcers or bleeding.
"Ten to 20 percent of women aged 50 and older use NSAIDs on a regular basis," Harris said. "Not only are these drugs potentially important for breast cancer prevention and control, they may also have significant value in the prevention and therapy of other cancers, too, such as cancers of the colon, lung and prostate."
This research was supported in part by Searle Research and Development, St. Louis, the manufacturer of celecoxib, and in part by Ohio State. (the Center of Molecular Epidemiology and Environmental Health, the Comprehensive Cancer Center, the School of Public Health and the Department of Surgery.)
Harris conducted the research with Galal Alshafie, a graduate student in the School of Public Health at Ohio State; Hussein Abou-Issa, an associate professor of surgery at Ohio State; and Karen Seibert, director of COX-2 research at Searle Monsanto Research and Development.
Contact: Randall Harris, 614-293-3903; Harris.44@osu.edu Cancer Research
Written by Holly Wagner, 614-292-8310; Wagner.235@osu.edu
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