The role of melatonin as an adjuvant therapeutic strategy in the modulation of carcinogenesis. A narrative review

Melatonin (N -acetyl -5 methoxytryptamine) is an indolic compound present in almost all fungi, plants, and animals. This neurohormone is synthesized and secreted into the internal environment mainly by the pineal gland, present in most vertebrates. Non -endocrine extrapineal locations have not been documented. This molecule with pleiotropic bioactions regulates the circadian rhythm, antioxidant, anti-inflammatory, immunostimulant, cardioprotective, antidiabetic, antiobesity, neuroprotective, and antiaging actions. Furthermore, in recent years, many studies have described the key role of melatonin in the prevention and development of cancer. The objective of this narrative review is to describe the different mechanisms through which melatonin exerts its action as an adjuvant in the modulation of carcinogenesis. The general anticarcinogenic mechanisms include epigenetic control, modulation of cell proliferation, regulation of cell cycle, induction of apoptosis, and telomerase inhibition. Melatonin also exerts antiestrogenic activity, which is particularly significant in hormone -dependent tumors, regulating the expression and transactivation of the estrogen receptor, and modulating the enzymes involved in the local synthesis of estrogens. Modulation of metastasis by melatonin includes increased expression of cell adhesion molecules such as E-cadherin and beta 1-integrin, inhibition of angiogenesis, and control of fat metabolism by inhibiting the uptake of fatty acids by membrane transporters. Finally, immunomodulatory properties include enhanced production of antiinflammatory interleukins and other cytokines in lymphocytes and monocytes and modulation of antioxidant activity by neutralizing free radicals. Despite all the mentioned properties, the use of melatonin in daily clinical practice is very limited, and additional studies are needed to better establish the role of this hormone in oncological clinical applications against different types of cancer.