Melanoma is a leading cause of cancer deaths worldwide. Although targeted therapy and immunotherapy have improved the outcome of patients with metastatic disease, unwanted side effects are a problem. Herein, by using human melanoma cell lines in vitro, we explore that melatonin enhances anti-tumor activity of commonly used BRAF/MEK inhibitors, i.e. vemurafenib (VF) and cobimetinib (CB), respectively. Our results have demonstrated that compared with VF/CB alone, melatonin significantly reduced proliferation read-outs (colony assay, drop assay) and induced of apoptosis (cleaved Casp-3, PARP) in melanoma cells. Concurrently, VF/CB+melatonin decreased melanoma invasiveness-related protein (E-cadherin), inducible nitric oxide synthase (iNOS), epithelial cell adhesion molecule (EpCAM), and proliferating cell nuclear antigen (PCNA); important players in melanoma tumorgenesis, tumor growth, invasion and metastasis. In addition, we also found that the combined treatment caused significant mechanistic changes in cellular bioenergetics by (i) uncoupling of oxidative phosphorylation (OXPHOS), (ii) attenuation of glycolysis (Seahorse assessment), (iii) dissipation of mitochondrial transmembrane potential (mtΔΨ) (FACS), and (iv) changes in mitochondrial morphology (TEM). Our results extend previously published data and they provide new perspectives and evidence for introduction of melatonin as an add-on complementary therapy in future treatment of melanoma-affected patients.

ESDR484 - Melatonin induces melanoma cell death and synergizes with BRAF/MEK inhibitors by altering cell bioenergetics

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.