Melatonin and Cancer Hallmarks

Abstract

Melatonin is a natural indoleamine produced by the pineal gland that has many functions, including regulation of the circadian rhythm. Many studies have reported the anticancer effect of melatonin against a myriad of cancer types. Cancer hallmarks include sustained proliferation, evading growth suppressors, metastasis, replicative immortality, angiogenesis, resisting cell death, altered cellular energetics, and immune evasion. Melatonin anticancer activity is mediated by interfering with various cancer hallmarks. This review summarizes the anticancer role of melatonin in each cancer hallmark. The studies discussed in this review should serve as a solid foundation for researchers and physicians to support basic and clinical studies on melatonin as a promising anticancer agent.

A pilot randomized controlled trial to improve sleep and fatigue in children with central nervous system tumors hospitalized for high‐dose chemotherapy

“…In our patients who self‐donate stem cells, even sleep prior to bone marrow harvest may be important for the recovery of blood counts post‐HDCT/aSCR. In addition, melatonin, a hormone of the pineal gland that helps regulate sleep–wake cycles, is a powerful free radical scavenger with oncostatic activity . In preclinical and clinical studies, melatonin supplementation was shown to improve stem cell survival in recipients, and to ameliorate damage to multiple organs from radiation and HDCT .…”

Melatonin: A promising agent targeting leukemia

“…In an in vitro study, melatonin suppressed the growth of human cancer cell lines by inhibition of specific phases of cell cycles. Also, melatonin decreases metastasis and invasion by changing the expression of adhesion molecules and intracellular communication . Other oncostatin actions of melatonin in various cancers include the modulation of transactivation and expression of estrogen receptor (ERa), calcium/calmadulin and protein kinase C activity, cytoskletal structure, redox status of cells, the activity of aromatase and telomerase, and fatty acid transportation and metabolism …”

“…Melatonin has been demonstrated to relieve many cancer complications such as angiogenesis, tumor proliferation, and metastasis. 67,68 Melatonin exhibits anticancer features through many functions including inhibition of fatty acids and growth factor uptake by tumor cells, suppression of the activity of telomerase (via decreasing the length of telomere), induction of apoptosis, inhibition of endothelin-1 synthesis (which is an angiogenic factor), increased growth of blood vessels, and regulation of some tumor suppressors' expression, such as TP53. 69,70 A large number of in vitro and in vivo studies have confirmed the antitumor properties of melatonin.…”

“…Also, melatonin decreases metastasis and invasion by changing the expression of adhesion molecules and intracellular communication. 68,77,78 Other oncostatin actions of melatonin in various cancers include the modulation of transactivation and expression of estrogen receptor (ERa), calcium/calmadulin and protein kinase C activity, cytoskletal structure, redox status of cells, the activity of aromatase and telomerase, and fatty acid transportation and metabolism. 70,[79][80][81][82] Besides the direct action of melatonin, this agent enables neutralizing free radicals through induction of suppression of redox enzyme activity (DUOX1&2, NOX2&4, iNOS, and mitochondria derived ROS) or antioxidant enzymes.…”

Melatonin Attenuates Endothelial-to-Mesenchymal Transition of Glomerular Endothelial Cells via Regulating miR-497/ROCK in Diabetic Nephropathy

“…Melatonin possesses multiple pathophysiological properties, including circadian rhythm regulation, antioxidant activity, immune defense, and inflammation and cancer prevention [7,8]. Accumulating evidence has suggested that melatonin's antioxidant activity might be useful in treating diabetes and attenuating diabetic nephropathy [9,10].…”