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

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

Publication date: Oct 07, 2019

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.

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.

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.

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.

Bustamante, P., Miyamoto, D., Goyeneche, A., de Alba Graue, P.G., Jin, E., Tsering, T., Dias, A.B., Burnier, M.N., and Burnier, J.V. Beta-blockers exert potent anti-tumor effects in cutaneous and uveal melanoma. 24384. 2019 Cancer Med.

Concepts Keywords
Adjuvant Therapy Beta blockers
Adrenoceptors Drugs
Apoptosis Scottish inventions
Beta Blocker RTT
CM Clinical medicine
Enucleated Adjuvant therapy
Epithelioid Potent anti tumor
Immunohistochemical Group cancers
Liver Tumor
Melanoma Liver metastases
Metastases Uveal melanoma
Propranolol Propranolol
Spindle Adjuvant therapy
Tumor DecisionDx-UM
Uveal Melanoma Apoptosis
VEGF

Semantics

Type Source Name
pathway BSID Apoptosis
gene UNIPROT VEGFA
drug DRUGBANK Propranolol
gene UNIPROT DNMT1
gene UNIPROT CD69
disease MESH growth
pathway BSID Adrenoceptors
disease MESH disease progression
disease MESH metastases
disease DOID cutaneous melanoma
pathway BSID Melanoma
disease DOID Melanoma
disease MESH Melanoma
disease DOID uveal melanoma
disease MESH uveal melanoma
disease MESH tumor

Original Article

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