Dopamine, a drug currently used to treat Parkinson's disease and other illnesses, also might work in cancer patients. The study, which was done in mouse and laboratory models, shows that dopamine could possibly prevent new blood vessels from growing and as a result, slow cancer progression.
Dopamine is a neurotransmitter in the brain that regulates movement and affects behavior. In its synthetic form, dopamine is used to treat heart attack victims, Parkinson's disease and pituitary tumors. But it wasn't known until now that dopamine worked by blocking the growth of new blood vessels (a process called angiogenesis).
"Researchers now can test this concept in solid tumors where angiogenesis plays a critical role in the growth and progression of these cancers," says Sujit Basu, M.D., Ph.D., a Mayo Clinic scientist who conducted this study with Partha Sarathi Dasgupta, Ph.D., a scientist with the Chittaranjan National Cancer Institute (CNCI) in Calcutta, India.; and, Debanjan Chakroborty, Ph.D., a postdoctoral fellow in biochemistry at Mayo Clinic and CNCI.
"Sometimes new drugs may not be the answer. We looked instead at a novel use for an established product and have found very promising results," Dr. Basu says.
The study has not been replicated in humans, but the results are encouraging, he says.
Dr. Basu has been studying the role of dopamine in cancer for years, and was credited with the initial discovery that dopamine can block new blood vessel growth. His current study is based on mouse and laboratory models of sarcoma -- a malignant tumor affecting soft tissues. The research is the first report that dopamine has a role in cancer's use of endothelial progenitor cells to provide a supply line of nourishing blood, Dr. Basu says. These cells, a form of stem cells, are released by bone marrow into the blood system in response to the vascular endothelial growth factor-A (VEGF-A), which is a protein that is secreted by oxygen-deprived cancer cells. The endothelial progenitor cells then help form new blood vessels to feed the cancer.
Researchers discovered that dopamine stops the transfer of endothelial progenitor cells from the bone marrow into the circulatory system by binding to a specific receptor on the surface of the progenitor cells. This binding suppresses the activity of matrix metallopeptidase 9 (MMP-9), an enzyme that enables these cells to move out of bone marrow.
In their experiments, they found that treatment with dopamine significantly decreased mobilation of the progenitor cells from the bone marrow, and it also decreased MMP-9 expression.
"This is the first time it has been shown that an important neurotransmitter like dopamine is regulating the mobilization of these progenitor cells from the bone marrow. This is very important and represents why these findings are so unique," Dr. Basu says.
This research was published in the March 13 online issue of The Journal of Clinical Investigation. Other authors include: Chandrani Sarkar, Ph.D., of both CNCI and Mayo Clinic; Uttio Roy Chowdhury, Ph.D., and Rathindranath Baral, Ph.D., both of CNCI.
This research was supported by grants from the Department of Biotechnology, the Government of India; the National Institutes of Health; and the U.S. Department of Defense.
Note: Cost of Dopamine (Mayo Clinic Pharmacy, March 6, 2008) Dopamine: 55 cents per dose (200 milligrams dopamine hydrochloride per 5 milliliters of solution)
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