Dopamine is a safe anti-angiogenic drug which can also prevent 5-fluorouracil induced neutropenia

The role of vascular endothelial growth factor - A (VEGFA) in tumor angiogenesis is well established and accordingly, molecules targeting VEGFA or its receptors are being presently used in the clinics for treatment of several types of cancer. However, these anti-angiogenic agents are expensive and have serious side effects. Thus identification of newer drugs with manageable systemic side effects or toxicities is of immense clinical importance. Since we have reported earlier that dopamine (DA) inhibits VEGFA induced angiogenesis in experimental tumor models, we therefore sought to investigate whether DA treatment results in similar toxicities like other anti-angiogenic agents. Our results indicated that unlike sunitinib, another commonly used anti-angiogenic agent in the clinics which targets VEGF receptors, DA (50mg/kg/d × 7days i.p.) not only could inhibit tumor angiogenesis and growth of HT29 human colon cancer and LLC (Lewis lung carcinoma) in mice, it also did not cause hypertension, hematological, renal and hepatic toxicities in normal, HT29 and LLC tumor bearing animals. Furthermore and interestingly, in contrast to the currently used anti-angiogenic agents, DA also prevented 5-fluorouracil (5FU) induced neutropenia in HT29 colon cancer bearing mice. This action of DA was through inhibition of 5FU mediated suppression of CFU-GM colony forming units in the bone marrow. Thus our results indicate that DA may be safely used as an anti-angiogenic drug for the treatment of malignant tumors.