Metabolic reprogramming characterized by alterations in nutrient uptake and critical molecular pathways associated with cancer cell metabolism represents a fundamental process of malignant transformation. Melatonin (N-acetyl-5-methoxytryptamine) is a hormone secreted by the pineal gland. Melatonin primarily regulates circadian rhythms but also exerts anti-inflammatory, anti-depressant, antioxidant and anti-tumor activities. Concerning cancer metabolism, melatonin displays significant anticancer effects via the regulation of key components of aerobic glycolysis, gluconeogenesis, the pentose phosphate pathway (PPP) and lipid metabolism. Melatonin treatment affects glucose transporter (GLUT) expression, glucose-6-phosphate dehydrogenase (G6PDH) activity, lactate production and other metabolic contributors. Moreover, melatonin modulates critical players in cancer development, such as HIF-1 and p53. Taken together, melatonin has notable anti-cancer effects at malignancy initiation, progression and metastasing. Further investigations of melatonin impacts relevant for cancer metabolism are expected to create innovative approaches supportive for the effective prevention and targeted therapy of cancers.

Biomedical Centre Martin Jessenius Faculty of Medicine in Martin Comenius University in Bratislava Mala Hora 4D 036 01 Martin Slovakia

Biomedical Research Centre Slovak Academy of Sciences 81439 Bratislava Slovakia

Clinic of Obstetrics and Gynecology Jessenius Faculty of Medicine Comenius University in Bratislava 03601 Martin Slovakia

Department of Animal Physiology Institute of Biology and Ecology Faculty of Science P J Šafarik University 04001 Košice Slovakia

Department of Applied Ecology Faculty of Environmental Sciences Czech University of Life Sciences Prague Kamýcká 129 165 00 Prague Czech Republic

Department of Medical Biology Jessenius Faculty of Medicine Comenius University in Bratislava 03601 Martin Slovakia

Department of Pathology St Elizabeth Cancer Institute Hospital 81250 Bratislava Slovakia

Department of Physiology and Biophysics Weill Cornell Medicine Qatar Education City Qatar Foundation Doha P O Box 24144 Qatar

European Association for Predictive Preventive and Personalised Medicine EPMA 1160 Brussels Belgium

Musculoskeletal Research Group and Tumour Biology Chair of Vegetative Anatomy Institute of Anatomy Faculty of Medicine Ludwig Maximilian University Munich D 80336 Munich Germany

Museum of Literature in Moravia Klašter 1 66461 Rajhrad Czech Republic

Predictive Preventive and Personalised Medicine Department of Radiation Oncology University Hospital Bonn Rheinische Friedrich Wilhelms Universität Bonn 53127 Bonn Germany

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