Melatonin anticancer effects: review

Abstract

Melatonin (N-acetyl-5-methoxytryptamine, MLT), the main hormone produced by the pineal gland, not only regulates circadian rhythm, but also has antioxidant, anti-ageing and immunomodulatory properties. MLT plays an important role in blood composition, medullary dynamics, platelet genesis, vessel endothelia, and in platelet aggregation, leukocyte formula regulation and hemoglobin synthesis. Its significant atoxic, apoptotic, oncostatic, angiogenetic, differentiating and antiproliferative properties against all solid and liquid tumors have also been documented. Thanks, in fact, to its considerable functional versatility, MLT can exert both direct and indirect anticancer effects in factorial synergy with other differentiating, antiproliferative, immunomodulating and trophic molecules that form part of the anticancer treatment formulated by Luigi Di Bella (Di Bella Method, DBM: somatostatin, retinoids, ascorbic acid, vitamin D3, prolactin inhibitors, chondroitin-sulfate). The interaction between MLT and the DBM molecules counters the multiple processes that characterize the neoplastic phenotype (induction, promotion, progression and/or dissemination, tumoral mutation). All these particular characteristics suggest the use of MLT in oncological diseases.

Figure 1

Insoluble in water (A), melatonin (MLT) dissolves in ethyl alcohol. Since absorption and bio-availability are linked with solubility, in the Luigi Di Bella formulation it is combined with a hydrogen bond to adenosine (B), thus becoming perfectly soluble and absorbable, with its biological-functional activities being reinforced. (Copyright Di Bella Foundation).

Figure 2

Anticancer action of melatonin: main molecular mechanisms. (1) Direct anti-oxidant enzyme activation; (2): bind with ML3 receptor; (3) direct antioxidant activity (scavenger); (4) gene expression regulation (differentiation); (5) calmodulin degradation: antiproliferative; (6) AC inhibition: antiproliferative. ML1/2: melatonin type receptor 1-2; SOD: super oxide dismutase; GRS: glutatione reductase; CAT: catalase; ML3/QR3: melatonin type receptor 3/quinone reductase 2; AC: adenylate ciclase; ROS: reactive oxygen species; RNS: reactive natrium species; AFMK: N(1)-acetyl-N(2)-formyl-5-methoxykynuramine. (Copyright Di Bella Foundation).