Metabolic Anti-Cancer Effects of Melatonin: Clinically Relevant Prospects

Samec, Marek; Liskova, Alena; Koklesova, Lenka; Zhai, Kevin; Varghese, Elizabeth; Samuel, Samson Mathews; Sudomova, Miroslava; Lucansky, Vincent; Kassayova, Monika; Pec, Martin; Biringer, Kamil; Brockmueller, Aranka; Kajo, Karol; Hassan, Sherif T. S.; Shakibaei, Mehdi; Golubnitschaja, Olga; Busselberg, Dietrich und Kubatka, Peter (2021): Metabolic Anti-Cancer Effects of Melatonin: Clinically Relevant Prospects. In: Cancers, Bd. 13, Nr. 12, 3018

Abstract

Simple Summary Metabolic reprogramming is required for both malignant transformation and tumor development, including invasion and metastasis. Melatonin (5-methoxy-N-acetyltryptamine) is a methoxyindole that is synthesized in the pineal gland. Importantly, melatonin has anticancer effects by stimulating apoptosis, regulation of survival signaling, suppression of metastasis and angiogenesis and regulation of epigenetic modifications that contribute to malignant transformation. Furthermore, melatonin affects steps associated with the Warburg phenotype and suppresses the switch from oxidative phosphorylation to aerobic glycolysis through the regulation of critical enzymes and glucose transporters. Melatonin is involved in regulation of p53 and HIF-1, directly participate in signaling cascades that modulate aerobic glycolysis, gluconeogenesis, the tricarboxylic acid cycle and the pentose phosphate pathway. A significant impact of melatonin in the modulation of metabolic cascades represent a unique opportunity to inhibit pathways metabolic reprogramming. 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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Tiermedizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Sprache: Englisch