Effect of Propranolol on Angiogenic Factors in Human Hematopoietic Cell Lines in vitro

Background: Beta-adrenergic blocking agents have been broadly used for treatment of many cardiovascular diseases such as arterial hypertension and ischemic heart failure. Anti-tumoral, anti-inflammatory and anti-angiogenesis effects of propranolol (a non-selective beta-adrenergic blocker) have been shown. Angiogenesis (replenish of the pre-existing vascular networks) plays a critical role in some pathological conditions such as tumor expansion and metastasis. In this study, we investigated the effects of propranolol on vascular endothelial growth factor (VEGF) production and matrix metalloproteinase-2 (MMP-2) activity (two important angiogenic factors) in human leukemic cell lines in vitro. Methods: Two human leukemic T (Molt-4 and Jurkat) and one monocyte (U937) cell lines were used in this study. The cells were cultured in complete RPMI medium and then incubated with different concentrations of propranolol (0.3-30 µM) in the presence or absence of phorbol myristate acetate (PMA, 25 ng/ml) for 48 hours. The level of VEGF secreted in the cell culture supernatants was measured with enzyme-linked immunosorbent assay kits (R and D systems) and MMP-2 activity in cell-conditioned media was evaluated by gelatin zymography. Results: Propranolol significantly decreased VEGF production and also MMP-2 activity in PMA-activated human leukemic cell lines Molt-4, Jurkat and U937 at 30 µM concentration of the drug compared to untreated control cells (P<0.05). Conclusion: Propranolol might be a useful anti-angiogenic agent in hematopoietic malignancies. Thus, propranolol along with its chronic long-term usage in cardiac problems may have potential implication in treatment of leukemia.