Use of Melatonin in Cancer Treatment: Where Are We?

Abstract

Cancer represents a large group of diseases accounting for nearly 10 million deaths each year. Various treatment strategies, including surgical resection combined with chemotherapy, radiotherapy, and immunotherapy, have been applied for cancer treatment. However, the outcomes remain largely unsatisfying. Melatonin, as an endogenous hormone, is associated with the circadian rhythm moderation. Many physiological functions of melatonin besides sleep–wake cycle control have been identified, such as antioxidant, immunomodulation, and anti-inflammation. In recent years, an increasing number of studies have described the anticancer effects of melatonin. This has drawn our attention to the potential usage of melatonin for cancer treatment in the clinical setting, although huge obstacles still exist before its wide clinical administration is accepted. The exact mechanisms behind its anticancer effects remain unclear, and the specific characters impede its in vivo investigation. In this review, we will summarize the latest advances in melatonin studies, including its chemical properties, the possible mechanisms for its anticancer effects, and the ongoing clinical trails. Importantly, challenges for the clinical application of melatonin will be discussed, accompanied with our perspectives on its future development. Finally, obstacles and perspectives of using melatonin for cancer treatment will be proposed. The present article will provide a comprehensive foundation for applying melatonin as a preventive and therapeutic agent for cancer treatment.

CYP1B1: A Novel Molecular Biomarker Predicts Molecular Subtype, Tumor Microenvironment, and Immune Response in 33 Cancers

“…The melatonin is further metabolized into 6-hydroxymelatonin (6OH-MEL) by human cytochrome P450 family [ 4 ]. Evidence shows that various biological properties of melatonin, such as the circadian clock [ 5 , 6 , 7 ], sleep regulation [ 8 , 9 ], anti-inflammatory properties [ 10 , 11 , 12 ], immune modulation [ 13 , 14 , 15 ], and anti-cancer activities [ 16 , 17 , 18 ], have been well revealed. Nevertheless, the clinical and immunological function of the cytochrome P450 family in cancer remains unclear.…”

IL‐10‐induced STAT3/NF‐κB crosstalk modulates pineal and extra‐pineal melatonin synthesis

“…[74][75][76][77] Our findings then suggest that a reduction in IL-10 levels could induce an increase in pineal melatonin and its rhythm amplitude, as well as melatonin produced locally by non-phagocytic cells, which in solid tumors is associated with a better prognosis. 78,79 High levels of IL-10 are also observed and correlated with a worse prognosis in later phases in burn patients, 80 neurodegenerative diseases 81 such as Parkinson's disease, 82 ischemic stroke, 83 Huntington's disease, 84 and autoimmune diseases like lupus erythematosus 85 and rheumatoid arthritis. 86 Interestingly, the circadian rhythm of melatonin is also impaired in these pathological conditions.…”

Beneficial Effects of Melatonin on Periodontitis Management: Far More Than Oral Cavity

“…Melatonin is mainly produced and released by the pineal gland, and is synthesized by other extrapineal tissues as well, such as heart, liver, placenta, kidney, gut, and bone marrow [ 89 , 90 ]. The biosynthesis and secretion pattern of melatonin and its application to cancer treatment have been reviewed by us recently [ 91 ]. So, the current review mainly focuses on the latest evidence for the protective role of melatonin in the pathogenesis of periodontitis, and the biological functions of melatonin that may be involved in periodontal treatment.…”