Molecular effect of propranolol on cell viability of hemangioma-derived stem cells (HemSCs)

Objectives: Propranolol (PRN) was found by chance very effective in treating hemangioma, yet the therapeutic mechanism remains unclear. This study was aimed to investigate the therapeutic mechanism of propranolol on hemangioma. Materials and Methods: The plasma propranolol concentrations at 2, 6, 10, 24 h were assayed by reversed phase high performance liquid chromatography (RP-HPLC) after oral administration of propranolol (1 mg/kg·d) once a day (qd, n=6) or twice a day (bid, n=6); The hemangioma-derived stem cells (HemSCs) were isolated from Chinese IH patients. The effect of propranolol on proliferation, apoptosis rate of HemSCs was observed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method and bi-fluorescence flow cytometry (FCM). With real-time PCR and Western blot, expression of vascular endothelial growth factor (VEGF) was observed after treatment with different concentrations (0, 0.02, 0.2, 2, 20 μM) of PRN at different times. Results: The peak propranolol concentrateion reached at 2 h in both qd group (207.8±33.9 ng/mL) and bid group (155.2±40.6 ng/ mL), the elimination half-life (t1/2) was longer than 6 h. The mean concentration of 10 h was significantly decreased in qd group, while that was elevated in bid group. The proliferation and total apoptosis rate of HemSCs was not obviously affected by PRN in normal concentration; but the expression of VEGF in HemSC was suppressed by PRN. Conclusions: PRN can inhibit HemSC to express VEGF, but cannot inhibit proliferation or induce apoptosis of HemSCs.