Dopamine is an inexpensive drug that also blocks the formation of tumor blood vessels.
This animal study suggests that dopamine lacks the serious side effects associated with currently used anti-angiogenic drugs, providing evidence for its use in humans.
A new study led by scientists at The Ohio State
University Comprehensive Cancer Center – Arthur G. James Cancer Hospital
and Richard J. Solove Research Institute (OSUCCC – James) suggests that
dopamine – an inexpensive drug currently used to treat heart, vascular
and kidney disorders – can be safely used in cancer treatment to curb
the growth of blood vessels in tumors.
Reporting in the International Journal of Cancer,
the researchers show that dopamine prevented the growth of blood
vessels in two animal models without causing many of the serious side
effects of the far-more expensive anti-angiogenic drugs currently used
in cancer therapy.
Furthermore, the agent prevented the drop in the number of
neutrophils (i.e., neutropenia) found in the blood that is typically
caused by 5-fluorouracil, a chemotherapy agent commonly used in the
treatment of gastrointestinal and other tumors, such as colon, stomach,
pancreas and breast cancers.
“In this study, we demonstrate for the first time that the
inexpensive drug dopamine lacks the serious side toxicities commonly
seen with the anti-angiogenesis drugs presently used in the clinic,”
says principal investigator Sujit Basu, MD, PhD, professor of pathology
and of medical oncology at the OSUCCC – James. “Furthermore, dopamine
can prevent the low-neutrophil count that is often induced by a very
common anti-cancer drug used for the treatment of gastrointestinal
cancers.
“Finally, because dopamine is being used in the clinics for other
disorders, our findings can be rapidly transferred to the clinic for the
treatment of cancer patients.”
Earlier studies by Basu and others have shown that dopamine blocks
the growth of new blood vessels in tumors by inhibiting the action of
vascular endothelial growth factor-A (VEGF-A).
“VEGF-A-induced angiogenesis plays a critical role in the
initiation, growth and progression of solid tumors, and the majority of
the anti-angiogenic drugs currently used in the clinics have anti-VEGF-A
actions,” Basu says. “Our study will help to rapidly translate the use
of this inexpensive but effective anti-angiogenic drug, dopamine, for
the treatment of cancer in the clinics.”
Basu and his colleagues conducted this study using an animal model
of human colon tumors transplanted into mice and a mouse model of lung
cancer. The technical findings included:
- Dopamine did not cause hypertension or affect liver functions (i.e., levels of alanine aminotransferase and aspartate aminotransferase were not elevated, as can happen with currently available anti-VEGF drugs);
- Renal function was unaffected by dopamine treatment; serum blood urea nitrogen (BUN) levels remained normal in both animal models and in normal animals, while animals treated with the anti-angiogenic inhibitor sunitinib showed increased levels;
- Dopamine administration did not affect platelet or neutrophil counts, although both were decreased by treatment with sunitinib.
- Dopamine prevented neutropenia (low neutrophil count) induced by 5-FU, an anti-cancer drug commonly used to treat gastrointestinal cancers.
Funding from the National Cancer Institute (grant CA124763) supported this research.
Other researchers involved in this study were Chandrani Sarkar and
Debanjan Chakroborty of The Ohio State University; and Partha Sarathi
Dasgupta, Chittaranjan National Cancer Institute, Kolkata, India.
The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
strives to create a cancer-free world by integrating scientific
research with excellence in education and patient-centered care, a
strategy that leads to better methods of prevention, detection and
treatment. Ohio State is one of only 41 National Cancer Institute
(NCI)-designated Comprehensive Cancer Centers and one of only four
centers funded by the NCI to conduct both phase I and phase II clinical
trials. The NCI recently rated Ohio State’s cancer program as
“exceptional,” the highest rating given by NCI survey teams. As the
cancer program’s 306-bed adult patient-care component, The James is a
“Top Hospital” as named by the Leapfrog Group and one of the top cancer
hospitals in the nation as ranked by U.S.News & World Report.