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.
Highlights
Melatonin (N-acetyl-5-methoxytryptamine) is an indoleamine produced by humans and otherMelatonin (N-acetyl-5-methoxytryptamine) is an indoleamine produced by humans and other animals in response to darkness
The objective of this review is to summarize the research on the anticancer effects of melatonin and to discuss the mechanisms activated by this hormone to inhibit each cancer hallmark
Mutations in tumor suppressor genes were observed in cancer cells with the most frequently mutated tumor suppressor gene is p53 followed by phosphatase and tensin homolog (PTEN), adenomatous polyposis coli (APC), ataxia-telangiectasia mutated (ATM), breast cancer gene2 (BRCA2), Von Hippel-Lindau (VHL), retinoblastoma (RB), cyclin-dependent kinase inhibitor 2A (CDKN2A), breast cancer gene2 (BRCA1) and Wilms tumor (WT1)
Summary
Melatonin (N-acetyl-5-methoxytryptamine) is an indoleamine produced by humans and other. The main producer of this hormone is the pineal gland and it is produced in several organs like the gastrointestinal tract, skin, retina, and bone marrow [1,2]. The relationship between melatonin and cancer has been investigated during the last 80 years and several epidemiological studies support the anticancer activities of this hormone [9,10]. The concept of cancer hallmarks was first proposed in 2000 by Hanahan and Weinberg. Many studies have explained the anticancer activities of melatonin This hormone can exert its anticancer effect through receptor-dependent and receptor-independent mechanisms [10]. The receptor-independent anticancer effects of melatonin involve diverse mechanisms including apoptosis induction, angiogenesis inhibition, immune evasion, and altered cancer metabolism [23,24]. Melatonin was used as adjuvant therapy to augment the anticancer effects of different agents [25,26,27]
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