Exercise and Antidepressants May Counteract Stress-induced Tumor Growth

Division of Cancer Control and Population Sciences

Higher levels of physical activity following the diagnosis of cancer have been associated with reduced rates of cancer recurrence. Physical activity has also been demonstrated to have antidepressant effects, benefiting individuals who are chronically stressed, including ovarian cancer patients.

“Because chronic stress contributes to aggressive tumor growth and results in a poor outcome for cancer patients, we predict that changes in behavior that reduce chronic stress may also slow tumor growth,” said Rosemarie Schmandt, Ph.D., associate professor, Department of Gynecologic Oncology, University of Texas, M.D. Anderson Cancer Center. “We expect that the same molecular pathways activated by physical activity and antidepressants that reduce stress will also inhibit stress- mediated tumor growth.”

With NCI funding*, “we’re trying to understand the molecular biology that underlies the beneficial effect of physical activity for cancer patients,” Dr. Schmandt explained. “That’s what we’re looking at now using a mouse model of ovarian cancer.” Dr. Schmandt has conducted a series of studies in mice, with the first series comparing the impact of exercise on ovarian tumor growth in stressed and unstressed mice and the second study looking at the effects of the antidepressant fluoxetine on tumors in stressed and unstressed mice. In her experiments, tumors in chronically stressed animals grew to approximately twice the size as those in unstressed animals. Both exercise and the drug held ovarian tumor growth in check in the stressed animals to roughly the same size as the smaller tumors in unstressed mice, she reported.

At a molecular level, she predicts that these effects are modulated by the circuits inside the cells that are affected by brain derived neurotrophic factor (BDNF). This protein is produced in response to either antidepressant drugs or exercise and is required for antidepressant behavioral effects. Dr. Schmandt says, “We know that in cultured ovarian cancer cells, exposure to a ‘mature’ version of the BDNF protein activates an enzyme called AMPK, which negatively regulates cell growth. It’s kind of a tumor suppressor pathway.”

“The really interesting thing is that our findings support the concept of ‘sound mind, sound body’,” Dr. Schmandt noted.

If her findings about the beneficial effects of physical activity and antidepressants in mice and cancer cell lines are eventually confirmed in human studies, it could be helpful for ovarian cancer patients. “Ideally, you’d like people to feel healthy enough after their cancer treatment to go out and begin or resume exercising,” Dr. Schmandt said. “However, if a patient doesn’t feel up to exercising everyday, like when they’re undergoing chemotherapy, having a drug they can use to carry them through until they feel able to exercise again would be a real advantage.”

For follow-up, “we’re expanding our study to look at obesity which may be contributing to tumor growth in the same way that chronic stress does,” she added. “Some of these studies are already underway in our lab. AMPK is known to be activated by exercise as well and by dietary restriction. We’re now looking at obesity as a kind of chronic stressor.”