April 10, 2007. Scientists have found evidence that the stress hormone epinephrine (also called adrenalin) causes changes in prostate and breast cancer cells that may make them resistant to treatment. Learning how to cope well with stress could play a role in preventing and treating the disease.
"This data implies that emotional stress may contribute to the development of cancer and may also reduce the effectiveness of cancer treatments," said George Kulik of Wake Forest University, the senior researcher on the project.
Epinephrine, which is produced by the adrenal glands, pumps out at sharply elevated levels in response to stressful situations and can remain continuously elevated during persistent stress and depression, according to previous research, Kulik says. The goal of the current study was to find out whether there is a direct link between stress hormones and changes in cancer cells.
Epinephrine has multiple effects on the body including changes in heart rate but previously knowledge of the effects of epinephrine on cancer has been limited.
Kulik and his team found evidence that epinephrine reduces sensitivity of cancer cells to the cancer-fighting process of apoptosis (programmed celled death). Aptosis in a healthy person prompts damaged or aging cells to self-destruct before they can grow into tumors. Even if cancer does develop, various treatments can help shrink tumors or limit growth and spread as long as apoptosis can be maintained or restored.
Studying prostate and breast cancer cells in the laboratory, Kulik and colleagues found that a protein called BAD -- which helps cause cell death -- becomes inactive when cancer cells are exposed to epinephrine. So apoptosis is blocked. Moreover, BAD became inactive (through a chemical process called phosphorylation) at levels of epinephrine concentrations found after acute and chronic psychosocial stress.
Anti-apoptotic signaling by epinephrine could be one of the mechanisms by which stress promotes tumorigenesis and decreases the efficacy of anti-cancer therapies, Kulik says.
"It may be important for patients who have increased responses to stress to learn to manage the effects," said Kulik. "The results point to the possibility of developing an intervention to block the effects of epinephrine," he added.
Kulik is now studying blood samples of prostate cancer patients to determine if there is a link between levels of stress hormones and severity of disease and has begun studying the effects of epinephrine in mice with prostate cancer.
Kulik's work's work adds to some previous evidence of links between stress and cancer, although studies in large groups of people have been mixed.
"Population studies have had contradictory results," said Kulik. "We asked the question, 'If stress is linked to cancer, what is the cellular mechanism?'
A team in Ohio found recently that norepinephrine, a related stress hormone, can stimulate tumor cells to produce compounds that break down the tissue around tumor cells and allow the cells to more easily move into the bloodstream. This was in ovarian cancer cells.
"A study from Canada showed that men who took beta blockers for hypertension for at least four years had an 18 percent lower risk of prostate cancer," said Kulik. "These drugs block the effects of epinephrine, which could explain the finding. Another study of men after radical prostatectomy reported increased mood disturbances, which are often associated with elevated stress hormones. Although these studies do not directly address the role of stress hormones, they suggest that stress hormones may play an important role in prostate cancer."
Support for this research came from the National Cancer Institute, the National Heart, Lung and Blood Institute, the Gilbert and Kathryn Mitchell Endowment and the OSU Comprehensive Cancer Center.
References:
Epinephrine protects cancer cells from apoptosis via activation of PKA and BAD phosphorylation [Abstract]
[full free text in .pdf download format]
J. Biol. Chem, 10.1074/jbc.M611370200
Konduru S.R. Sastry, Yelena Karpova, Sergey Prokopovich, Adrienne J. Smith, Brian Essau, Avynash Gersappe, Jonathan P. Carson, Michael J. Weber, Thomas C. Register, Yong Q. Chen, Raymond B. Penn, and George Kulik. Cancer Biology, Wake Forest University Health Sciences, Winston-Salem, NC 27157
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