Beta‐blockers exert potent anti‐tumor effects in cutaneous and uveal melanoma

Abstract

Abstract Background Melanoma is a life‐threatening group of cancers mainly affecting the skin (cutaneous melanoma, CM) and the eyes (uveal melanoma, UM). Nearly half of patients with UM develop liver metastases regardless of the primary treatment. For this reason, adjuvant therapy to prevent disease progression is essential to improve survival of patients with melanoma. Beta‐adrenoceptors (β‐AR) have emerged as novel targets to inhibit tumor growth and dissemination in CM, but have not been investigated in UM. Methods The aim of this study was to comprehensively evaluate the effects of a non‐selective β‐blocker in UM and CM. Propranolol was tested on four UM and two CM cell lines to determine the effects of this beta‐blocker. The expression of β‐AR in UM was assessed in enucleated eyes of 36 patients. Results The results showed that propranolol exerts potent anti‐proliferative effects, attenuates migration, reduces VEGF and induces cell cycle arrest and apoptosis in both UM and CM in a dose‐dependent manner. Furthermore, levels of cell‐free DNA released from the cells correlated to propranolol treatment and may be an indicator of treatment response. Finally, immunohistochemical analysis revealed the expression of β1 and β2 adrenoceptors in all UM patients, with higher expression seen in the more aggressive epithelioid versus less aggressive spindle cells. Conclusions Collectively our data suggest that a nonselective beta‐blocker may be effective against melanoma. For the first time, we show potent anti‐tumor effects in UM cells following propranolol administration and expression of β1 and β2 adrenoceptors in patient tissue.

Keywords

• adjuvant therapy
• beta‐blockers
• melanoma
• uveal melanoma