β-adrenergic receptor-dependent and -independent effects of propranolol in infantile hemangioma

Infantile hemangioma (IH) is the most common tumour of infancy. The recommended treatment for IH is a non-selective β-adrenergic receptor antagonist, propranolol. Although propranolol is effective in regressing hemangiomas, the mechanism of its action is poorly understood. Moreover, some hemangiomas regrow following cessation of treatment. We have recently shown that IH arise from multi-potent stem cells. Whether IH stem cells are responsive to propranolol is unknown and is the focus of this study. Hemangioma-derived stem cells and vascular endothelial cells were exposed to propranolol and were assayed for cellular and molecular alterations. Our studies show that propranolol inhibits the growth of hemangioma stem cells but does not cause apoptosis. We further show that the mechanism may involve serotonin receptors in hemangioma stem cells. These findings are in contrast to endothelial cells, which exhibit apoptosis potentially through the action of propranolol on β-adrenergic receptors. This study reveals that propranolol’s therapeutic effect is β-adrenergic receptor-independent in hemangioma-derived stem cells