Propranolol inhibits growth of hemangioma-initiating cells but does not induce apoptosis

Infantile hemangioma (IH) is the most common tumor of infancy. The first-line therapy for IH is propranolol, a nonselective β-adrenergic receptor antagonist. However, mechanisms for the therapeutic effect of propranolol and regrowth of IH following cessation of treatment in some cases are not clear. We have recently shown that IH arises from multipotent stem cells. Whether IH stem cells are responsive to propranolol and are selectively targeted is unknown, and this is the focus of this study.

This study reveals that propranolol does not induce apoptosis in IH stem cells, which is in contrast with the result for ECs. Escape from apoptosis in IH stem cells may involve induction of antiapoptotic pathways.

IH stem cells were exposed to propranolol and were assayed for cellular and molecular alterations. We used endothelial cells (ECs) as controls and bone marrow-derived mesenchymal progenitor cells (bm-MPCs) as normal stem/progenitor counterparts to determine selectivity.

Our results show that propranolol significantly reduced IH stem cell growth but failed to induce caspase-3 activation. Normal bm-MPCs and mature ECs showed maintained or increased caspase-3 activation and significantly reduced cyclin-D1 levels. We further show that IH stem cells may escape apoptosis by inducing antiapoptotic pathways.