Metabolic Anti-Cancer Effects of Melatonin: Clinically Relevant Prospects

• Published in: Cancers Vol. 13; no. 12; p. 3018
• Main Authors: Samec, Marek, Liskova, Alena, Koklesova, Lenka, Zhai, Kevin, Varghese, Elizabeth, Samuel, Samson Mathews, Šudomová, Miroslava, Lucansky, Vincent, Kassayova, Monika, Pec, Martin, Biringer, Kamil, Brockmueller, Aranka, Kajo, Karol, Hassan, Sherif T S, Shakibaei, Mehdi, Golubnitschaja, Olga, Büsselberg, Dietrich, Kubatka, Peter
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 16-06-2021; MDPI
• Subjects: Angiogenesis; Antioxidants; Antitumor agents; Apoptosis; Biosynthesis; Cancer; Circadian rhythms; Dehydrogenases; Endocrine system; Enzymes; Epigenetics; Free radicals; Genetic transformation; Gluconeogenesis; Glucose; Glucose metabolism; Glucose transporter; Glucosephosphate dehydrogenase; Glycolysis; Inflammation; Kinases; Lactic acid; Lipid metabolism; Malignancy; Melatonin; Metabolism; Metabolites; Metastases; Metastasis; Mutation; Nutrient uptake; Oxidative phosphorylation; Pentose phosphate pathway; Phenotypes; Review; Serotonin; Signal transduction; Sleep disorders; Tricarboxylic acid cycle; anti-tumor; predictive preventive personalized medicine (PPPM/3PM); antioxidant; anti-inflammatory; cancer; metabolism; mitochondrial dysfunction; anti-depressant; melatonin; Warburg effect
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers13123018

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.