Action Of Melatonin Research Articles

Melatonin: an endogenous miraculous indolamine, fights against cancer progression.

Melatonin is an amphipathic indolamine molecule ubiquitously present in all organisms ranging from cyanobacteria to humans. The pineal gland is the site of melatonin synthesis and secretion under the influence of the retinohypothalamic tract. Some extrapineal tissues (skin, lens, gastrointestinal tract, testis, ovary, lymphocytes, and astrocytes) also enable to produce melatonin. Physiologically, melatonin regulates various functions like circadian rhythm, sleep-wake cycle, gonadal activity, redox homeostasis, neuroprotection, immune-modulation, and anticancer effects in the body. Inappropriate melatonin secretion advances the aging process, tumorigenesis, visceral adiposity, etc. METHODS: For the preparation of this review, I had reviewed the literature on the multidimensional activities of melatonin from the NCBI website database PubMed, Springer Nature, Science Direct (Elsevier), Wiley Online ResearchGate, and Google Scholar databases to search relevant articles. Specifically, I focused on the roles and mechanisms of action of melatonin in cancer prevention. The actions of melatonin are primarily mediated by G-protein coupled MT1 and MT2 receptors; however, several intracellular protein and nuclear receptors can modulate the activity. Normal levels of the melatonin protect the cells from adverse effects including carcinogenesis. Therapeutically, melatonin has chronomedicinal value; it also shows a remarkable anticancer property. The oncostatic action of melatonin is multidimensional, associated with the advancement of apoptosis, the arrest of the cell cycle, inhibition of metastasis, and antioxidant activity. The present review has emphasized the mechanism of the anti-neoplastic activity of melatonin that increases the possibilities of the new approaches in cancer therapy.

Role and Therapeutic Potential of Melatonin in the Central Nervous System and Cancers

Melatonin (MLT) is a powerful chronobiotic hormone that controls a multitude of circadian rhythms at several levels and, in recent times, has garnered considerable attention both from academia and industry. In several studies, MLT has been discussed as a potent neuroprotectant, anti-apoptotic, anti-inflammatory, and antioxidative agent with no serious undesired side effects. These characteristics raise hopes that it could be used in humans for central nervous system (CNS)-related disorders. MLT is mainly secreted in the mammalian pineal gland during the dark phase, and it is associated with circadian rhythms. However, the production of MLT is not only restricted to the pineal gland; it also occurs in the retina, Harderian glands, gut, ovary, testes, bone marrow, and lens. Although most studies are limited to investigating the role of MLT in the CNS and related disorders, we explored a considerable amount of the existing literature. The objectives of this comprehensive review were to evaluate the impact of MLT on the CNS from the published literature, specifically to address the biological functions and potential mechanism of action of MLT in the CNS. We document the effectiveness of MLT in various animal models of brain injury and its curative effects in humans. Furthermore, this review discusses the synthesis, biology, function, and role of MLT in brain damage, and as a neuroprotective, antioxidative, anti-inflammatory, and anticancer agent through a collection of experimental evidence. Finally, it focuses on the effect of MLT on several neurological diseases, particularly CNS-related injuries.

Biorhythmic and receptor mediated interplay between melatonin and insulin: its consequences on diabetic erythrocytes

Diabetes mellitus, one of the crucial epidemics of this country has snatched the sleep of mankind with a steep slope of 108 million in 1980 to more than 460 million in today’s world. The global statistics based on numerological information from World Health Organization (WHO) proposed alarmingly about 642 million affected individuals by 2040. Type 1 diabetes is due to damaged pancreatic β-cells while type 2 diabetes is a result of insulin insensitivity associated with hyperglycaemia. Hyperglycaemia is a principal symptom of diabetes. As a result, the circulatory erythrocytes [red blood cells (RBCs)] become the first and most vulnerable victims to confront such a stressful environment. The RBCs possess many components including haemoglobin, membrane proteins and lipids. They prefer to interact with glucose and form glycated haemoglobin and membrane phospholipid asymmetry which alters RBC adherence. These alterations trigger intracellular reactive oxygen species (ROS) formation and oxidative damage in diabetic erythrocytes. Melatonin, an indoleamine, ameliorates oxidative stress in various tissues and has the capacity of shielding erythrocytes from deleterious stress. A crucial relationship between melatonin and insulin indicates their interplay in occurrence of diabetes. Biorhythm entrained and receptor mediated action of melatonin on pancreatic β-cells in the context of hyperglycaemia are discussed for the first time in the review. Since melatonin protects against erythrocytes, as well as beneficial to diabetes, it is worthy to address proficiency of this indoleamine to the diabetic erythrocytes. In summary, this review has discussed the fostering role of melatonin in hyperglycaemia and encouraged further investigation related to the molecular pathways of melatonin on glucose metabolism.

Chemoprotective Effect of Melatonin on Dmba/croton Oil Induced Carcinogenesis in Skin of Swiss Albino Mice

Melatonin, a hormone secreted by the pineal gland, is known to have anti-mutagenic, antioxidant and oncostatic functions. This beneficial action of melatonin has been explained in terms of its ability to scavenge free radicals and the activities of anti-oxidant enzymes. The present study was carried out to evaluate the anti-tumor activity of melatonin on the two stage process of skin carcinogenesis, A significant reduction in tumor incidence, tumor burden, tumor yield, and cumulative number of papilloma was observed in mice treated with 10mg/kg of melatonin as compared to the positive control group treated with DMBA plus croton oil. Furthermore, Histopathological alterations in the carcinogen-treated control animals were also observed in the form of epidermal hyperplasia, keratinized pearl formation, and acanthosis in skin and tumors, whereas these were found to be reduced significantly in melatonin group were administrated before DMBA administration. The results thus can be suggested that melatonin may function as an endogenous anti-mutagenic and oncostatic agent

MELATONIN MODULATES DYNAMICS OF PLANARIAN STEM CELL PROLIFERATION

Melatonin is a derivate of biogenic amine of serotonin identified in all classes of animals including flatworms. Melatonin demonstrates different physiological functions the main of which is circadian rhythm regulation. Via specific G-protein coupled receptors, melatonin affects the target cells changing the levels of other hormones. On early stages of embryonic development, biogenic amines as well as melatonin play a role of specific signal cell molecules that regulate processes of cellular renewal. This work has studied physiological function of melatonin in free-living flatworms, planarian Schmidtea mediterranea. The influence of melatonin on diurnal dynamics of stem cells proliferation was investigated using an immunocytochemical method and confocal laser scanning microscopy. The specific antibodies against H3 phosphohistones were applied for immunocytochemical identification of proliferative cells. It was shown that melatonin (1 µМ) decreased the total number of proliferative cells in planarians. It was also found that the diurnal dynamics of cells proliferation in planarians was changed by melatonin: regular rhythmic oscillations observed in the control group of animals were smoothening. Further researches are required to clarify mechanisms of melatonin actions.

Protective action of melatonin on diabetic rat testis at cellular, hormonal and immunohistochemical levels

The aim of the present study was to analyze the effects of melatonin treatment on diabetic rat testes. Fifty albino rats were divided into the following groups: CG: control group; GD: placebo-induced and placebo-treated mice; GDI: insulin-induced and post-confirmation diabetes-induced rats; GDM: diabetes-induced and melatonin-treated post-confirmation mice and GDMS: diabetes-induced and melatonin-treated mice simultaneously. Melatonin was administered at a dose of 10 mg/kg in drinking water every day for 20 days at night. Diabetes was induced by streptozotocin (60 mg/kg) and confirmed after the fifth day of induction. Insulin was administered at 5 IU (international units)/day at different times of the day for 20 days. The testes were submitted to histopathological, morphometric, immunohistochemical and oxidative stress analysis. Melatonin moderately decreased glycemic levels, protected weight loss and morphometric changes in the testicles, increased antioxidant enzyme levels and stabilized plasma testosterone and androgen receptor levels and decreased inflammatory markers in the testicles. Showing its potential to mitigate diabetes effects.

Utilizing Melatonin to Alleviate Side Effects of Chemotherapy: A Potentially Good Partner for Treating Cancer with Ageing.

Persistent senescence seems to exert detrimental effects fostering ageing and age-related disorders, such as cancer. Chemotherapy is one of the most valuable treatments for cancer, but its clinical application is limited due to adverse side effects. Melatonin is a potent antioxidant and antiageing molecule, is nontoxic, and enhances the efficacy and reduces the side effects of chemotherapy. In this review, we first summarize the mitochondrial protective role of melatonin in the context of chemotherapeutic drug-induced toxicity. Thereafter, we tabulate the protective actions of melatonin against ageing and the harmful roles induced by chemotherapy and chemotherapeutic agents, including anthracyclines, alkylating agents, platinum, antimetabolites, mitotic inhibitors, and molecular-targeted agents. Finally, we discuss several novel directions for future research in this area. The information compiled in this review will provide a comprehensive reference for the protective activities of melatonin in the context of chemotherapy drug-induced toxicity and will contribute to the design of future studies and increase the potential of melatonin as a therapeutic agent.

Therapeutic Algorithm for Use of Melatonin in Patients With COVID-19.

The coronavirus, COVID-19, has infected hundreds of thousands and killed tens of thousands of individuals worldwide. This highly infectious condition continues to ravage the world population and has yet to reach it peak infective rate in some countries. Many conventional drugs including hydroxychloroquine/chloroquine, lopinavir, remdesivir, etc., have been repurposed as treatments for this often deadly disease, but there is no specifically-designed effective drug available; also, the drugs mentioned have significant side effects and their efficacy is unknown. New drugs and vaccines are being designed as COVID-19 treatment, but their development and testing will require months to years. Time is not a luxury that this crisis has. Thus, there is a serious unmet need for the identification of currently-available and safe molecules which can be used to slow or treat COVID-19 disease. Here, we suggest melatonin be given consideration for prophylactic use or treatment alone or in combination with other drugs. Melatonin's multiple actions as an anti-inflammatory, anti-oxidant, and anti-viral (against other viruses) make it a reasonable choice for use. Melatonin is readily available, can be easily synthesized in large quantities, is inexpensive, has a very high safety profile and can be easily self-administered. Melatonin is endogenously-produced molecule in small amounts with its production diminishing with increased age. Under the current critical conditions, large doses of melatonin alone or in combination with currently-recommended drugs, e.g., hydroxychloroquine/chloroquine, to resist COVID-19 infection would seem judicious.

Hypotensive Action of Melatonin in Patients with Arterial Hypertension.

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Melatonin inhibits Th17 differentiation

Abstract Hypertension is a leading risk factor for cardiovascular disease, which is a major cause of death worldwide. T cells are required for the development of hypertension. Specifically, we showed that T helper 17 (Th17) cells produce the pro-inflammatory cytokine, IL-17A, which leads to sustained elevations of blood pressure and renal and vascular dysfunction in experimental hypertension. T cell differentiation and trafficking is regulated by circadian clocks. High fat and high salt intake, typical of Western diets, disrupt circadian rhythms and are associated with increased risk for developing cardiovascular disease. These diets are also associated with an increase in Th17 cell differentiation. Melatonin is a major circadian hormone with anti-inflammatory and anti-oxidant actions. To determine the interplay between circadian rhythms and Th17 cell differentiation, we tested the hypothesis that in vitro treatment of Th17 cells with melatonin would inhibit IL-17A cytokine production. Splenic naïve CD4+ T cells from wild type C57Bl/6J male mice were cultured for 72 hours on anti-CD3/anti-CD28 antibody coated plates in the presence or absence of Th17-polarizing cytokines and treated with melatonin (2ng/ml; Sigma Aldrich) or vehicle (0.02% DMSO). IL-17A cytokine levels were analyzed by ELISA. In cells treated with Th17 polarizing cytokines, IL-17A cytokine production was significantly reduced by melatonin. Thus, this study highlights the involvement of circadian control of Th17 cells via the actions of melatonin to suppress Th17 differentiation and IL-17A production. Future studies will determine the effect of melatonin treatment in vivo on development of hypertension and renal/vascular dysfunction.

Melatonin ameliorates ketoconazole-induced increase in thyroid function

Background&#x0D; The antithyroid effect of ketoconazole has been reported. The secretion and action of melatonin in the thyroid gland are also known. However, the possible effect of melatonin on ketoconazole-induced antithyroid effect is unknown.&#x0D; Objective&#x0D; We sought to investigate the modulatory effect of ketoconazole and/or melatonin on thyroid function in female rats.&#x0D; Methods&#x0D; Groups 1-4 of female rats respectively underwent 14-day treatment with normal saline, 25 mg/kg ketoconazole, 4 mg/kg melatonin and 10 mg/kg melatonin. Groups 5 and 6 both received 14-day treatment with ketoconazole and were respectively treated with 4 mg/kg melatonin and 10 mg/kg melatonin simultaneously. Groups 7 and 8 respectively underwent 14-day pretreatment with 4 mg/kg melatonin and 10 mg/kg melatonin, followed by 14-day administration of ketoconazole to both groups. Groups 9 and 10 were both treated with ketoconazole for 14 days, followed by respective 14-day administration of 4 mg/kg melatonin and 10 mg/kg melatonin.&#x0D; Results&#x0D; TSH, T3, T4, and iodine concentrations were increased by separate administration of ketoconazole and either dose of melatonin when compared to control. However, pre-treatment or post-treatment of ketoconazole-treated rats with melatonin abolished the ketoconazole-induced increase in TSH, T3, T4, and iodine while co-administration of ketoconazole with melatonin caused no improvement in the ketoconazole-induced increase in TSH, T3, and T4 except iodine concentration.&#x0D; Conclusion&#x0D; Ketoconazole increased thyroid function, which was ameliorated by pre- or post-treatment with melatonin, possibly via modulation of the iodination process.&#x0D; Keywords: Iodine; Ketoconazole; Melatonin; Thyroid function; Toxicity

Melatonin concentration in peripheral blood and melatonin receptors (MT1 and MT2) in the testis and epididymis of male roe deer during active spermatogenesis

Melatonin regulates male reproductive function in seasonal and non-seasonal breeder mammals. The presence of melatonin membrane receptors (MT1 and MT2) in the testis and epididymis has been demonstrated in several species. Wild roe deer are a short-day breeding species characterised by a short rutting season lasting from mid-July to mid-August. The aim of this study was to determine the concentration of melatonin in the peripheral blood and the presence of MT1 and MT2 receptors in the testis and epididymis in male roe deer during the pre-rut (May), rut (July/August) and post-rut (September) periods. The melatonin concentration was higher in May (522.50 ± 54.20 pg/mL) compared to July/August (258.50 ± 36.82 pg/mL; P < 0.05). During September, the melatonin concentration was higher (393.50 ± 36.77 pg/mL) than in July/August (P < 0.05) but lower than in May (P < 0.05). Immunohistochemical analysis showed the presence of MT1 and MT2 receptors in Leydig cells, Sertoli cells and germ cells in the testis, in addition to the epithelial cells of the epididymis caput, corpus and cauda. MT1 and MT2 receptor expression in the testis and epididymis, assessed by Western blot, was higher in May and July/August (when spermatogenic and steroidogenic activity restarts and reaches its peak, respectively) compared to September (when spermatogenic and steroidogenic activity decreases). This could indicate a stimulatory effect of melatonin on testicular (i.e., steroidogenesis and spermatogenesis) and epididymal (i.e., spermatozoa maturation) function in male roe deer through the MT1 and MT2 receptors. Our results form the basis for further studies into the detailed mechanism of action of melatonin through MT1 and MT2 receptors for optimal reproductive activity in male roe deer and other mammals.

T. cruzi infection among aged rats: Melatonin as a promising therapeutic molecule.

Although T. cruzi was identified as the cause of Chagas disease more than 100 years ago, satisfactory treatments still do not exist, especially for chronic disease. Here we review work suggesting that melatonin could have promise as a Chagas therapeutic. Melatonin has remarkably diverse actions. It is an immunomodulator, an anti-inflammatory, an antioxidant, a free radical scavenger, and has antiapoptotic and anti-aging effects. The elderly (aged 60 years or more) as a group are growing faster than any other age group. Here we discuss the major effects and the mechanisms of action of melatonin on aged T. cruzi-infected rats. Melatonin's protective effects may be consequences of its cooperative antioxidant and immunomodulatory actions. Melatonin modulates oxidative damage, inducing an antioxidant response and reversing age-related thymus regression. Its protective actions could be the result of its anti-apoptotic activity, and by its counteracting the excessive production of corticosterone. This review describes our work showing that host age plays an important and variable influence on the progression of systemic T. cruzi infection and supporting the hypothesis that melatonin should be considered as a powerful therapeutic compound with multiple activities that can improve host homeostasis during experimental T. cruzi infection.

Melatonin and organ transplantation: what is the relationship?

Melatonin has anti-inflammatory and antioxidant properties that can influence tissue growth and apoptosis. This aspect may influence the success of organ transplantation. To evaluate the relationship between melatonin and organ transplantation. A systematic review was performed in PubMed databases using the search terms: "melatonin physiology" or "melatonin therapy" and "transplant pharmacology" or "transplant physiology" or "transplant therapy" or "Transplant therapy". Experiments on the organs of the reproductive system were not included. After analysis, five articles were selected after reading the title and abstract of 50 manuscripts. The works were divided into two aspects: a) analysis of the influence of the organ transplantation procedure on melatonin production; b) action of melatonin on organ transplantation. The cardiac transplantation surgical procedure, immunosuppression, and graft did not influence melatonin secretion in rodents, but there was a significant reduction of melatonin in the renal transplantation procedure in patients with renal insufficiency. Melatonin administration in experimental models decreased rejection and improved transplant success. Studies show that melatonin can reduce organ and species dependence, and the use of melatonin decreases graft rejection.

New insights into antimetastatic signaling pathways of melatonin in skeletomuscular sarcoma of childhood and adolescence.

Melatonin is an indole produced by the pineal gland at night under normal light or dark conditions, and its levels, which are higher in children than in adults, begin to decrease prior to the onset of puberty and continue to decline thereafter. Apart from circadian regulatory actions, melatonin has significant apoptotic, angiogenic, oncostatic, and antiproliferative effects on various cancer cells. Particularly, the ability of melatonin to inhibit skeletomuscular sarcoma, which most commonly affects children, teenagers, and young adults, is substantial. In the past few decades, the vast majority of references have focused on the concept of epithelial-mesenchymal transition involvement in invasion and migration to allow carcinoma cells to dissociate from each other and to degrade the extracellular matrix. Recently, researchers have applied this idea to sarcoma cells of mesenchymal origin, e.g., osteosarcoma and Ewing sarcoma, with their ability to initiate the invasion-metastasis cascade. Similarly, interest of the effects of melatonin has shifted from carcinomas to sarcomas. Herein, in this state-of-the-art review, we compiled the knowledge related to the molecular mechanism of antimetastatic actions of melatonin on skeletomuscular sarcoma as in childhood and during adolescence. Utilization of melatonin as an adjuvant with chemotherapeutic drugs for synergy and fortification of the antimetastatic effects for the reinforcement of therapeutic actions are considered.

Melatonin alleviates cardiac fibrosis via inhibiting lncRNA MALAT1/miR-141-mediated NLRP3 inflammasome and TGF-β1/Smads signaling in diabetic cardiomyopathy.

Melatonin is a hormone produced by the pineal gland, and it has extensive beneficial effects on various tissue and organs; however, whether melatonin has any effect on cardiac fibrosis in the pathogenesis of diabetic cardiomyopathy (DCM) is still unknown. Herein, we found that melatonin administration significantly ameliorated cardiac dysfunction and reduced collagen production by inhibiting TGF-β1/Smads signaling and NLRP3 inflammasome activation, as manifested by downregulating the expression of TGF-β1, p-Smad2, p-Smad3, NLRP3, ASC, cleaved caspase-1, mature IL-1β, and IL-18 in the heart of melatonin-treated mice with diabetes mellitus (DM). Similar beneficial effects of melatonin were consistently observed in high glucose (HG)-treated cardiac fibroblasts (CFs). Moreover, we also found that lncRNA MALAT1 (lncR-MALAT1) was increased along with concomitant decrease in microRNA-141 (miR-141) in DM mice and HG-treated CFs. Furthermore, we established NLRP3 and TGF-β1 as target genes of miR-141 and lncR-MALAT1 as an endogenous sponge or ceRNA to limit the functional availability of miR-141. Finally, we observed that knockdown of miR-141 abrogated anti-fibrosis action of melatonin in HG-treated CFs. Our findings indicate that melatonin produces an antifibrotic effect via inhibiting lncR-MALAT1/miR-141-mediated NLRP3 inflammasome activation and TGF-β1/Smads signaling, and it might be considered a potential agent for the treatment of DCM.

Seasonal simulated photoperiods influence melatonin release and immune markers of pike perch Sander lucioperca

Melatonin is considered as the time-keeping hormone acting on important physiological functions of teleosts. While the influence of melatonin on reproduction and development is well described, its potential role on immune functions has little been considered. In order to better define an immune modulation by the melatonin hormone, we hypothesized that natural variations of photoperiod and subsequent changes in melatonin release profile may act on immune status of pikeperch. Therefore, we investigated during 70 days the effects of two photoperiod regimes simulating the fall and spring in western Europe, on pikeperch physiological and immune responses. Samples were collected at 04:00 and 15:00 at days 1, 37 and 70. Growth, plasma melatonin levels, innate immune markers and expression of immune-relevant genes in head kidney tissue were assessed. While growth and stress level were not affected by the seasonal simulated photoperiods, nocturnal levels of plasma melatonin were photoperiod-dependent. Innate immune markers, including lysozyme, complement, peroxidase and phagocytic activities, were stimulated by the fall-simulated photoperiod and a significant correlation was made with plasma melatonin. In addition to bring the first evidence of changes in fish immunocompetence related to photoperiod, our results provide an additional indication supporting the immunomodulatory action of melatonin in teleosts.

The role of melatonin on miRNAs modulation in triple-negative breast cancer cells

Melatonin, a hormone secreted by pineal gland, exerts antimetastatic effects by reducing tumor cell proliferation, migration and invasion. MicroRNAs (miRNAs) are small, non-coding RNAs that play a crucial role in regulation of gene expression and biological processes of the cells. Herein, we search for a link between the tumor/metastatic-suppressive actions of melatonin and miRNA expression in triple-negative breast cancer cells. We demonstrated that melatonin exerts its anti-tumor actions by reducing proliferation, migration and c-Myc expression of triple negative breast cancer cells. By using Taqman-based assays, we analyzed the expression levels of a set of miRNAs following melatonin treatment of triple negative breast cancer cells and we identified 17 differentially expressed miRNAs, 6 down-regulated and 11 up-regulated. We focused on the anti-metastatic miR-148b and the oncogenic miR-210 both up-regulated by melatonin treatment and studied the effect of their modulation on melatonin-mediated impairment of tumor progression. Surprisingly, when miR-148b or miR-210 were depleted in triple-negative breast cancer cells, using a specific miR-148b sponge or anti-miR-210, melatonin effects on migration inhibition and c-myc downregulation were still visible suggesting that the increase of miR-148b and miR-210 expression observed following melatonin treatment was not required for the efficacy of melatonin action. Nevertheless, ours results suggest that melatonin exhibit a compound for metastatic trait inhibition, especially in MDA-MB-231 breast cancer cells even if a direct link between modulation of expression of certain proteins or miRNAs and melatonin effects has still to be established.

Effects of melatonin on cardiovascular risk factors and metabolic syndrome: a comprehensive review.

Melatonin, as a neuroendocrine hormone, is produced primarily by the pineal gland. Melatonin, a pleotropic molecule, acts as a free radical scavenger, antioxidant, and regulator of circadian rhythm in mammals via several receptor-mediated and non-receptor-mediated mechanisms. This inexpensive, well-tolerated, and multi-target molecule has a great therapeutic potential against many diseases. Many evidences have proposed that melatonin plays a key role in the pathophysiology of various cardiovascular diseases. The aim of this paper is to discuss the data and experiments regarding the effects of melatonin in management of cardiovascular risk factors. PubMed, EMBASE, and Scopus have been searched for data collection using related keywords. Two hundred ten articles were included in this review from 2253 founded documents. Using these documents, the main mechanisms of action of melatonin are discussed and summarized in this article. Also, recent progresses regarding melatonin's effects on cardiovascular risk factors and diseases including diabetes, hypertension, hyperlipidemia, obesity, myocardial ischemia-reperfusion injury, pulmonary hypertension, and atherosclerosis have been reviewed. Many studies have demonstrated the beneficial effects of melatonin in prevention and improving cardiovascular risk factors, and this inexpensive and well-tolerated drug can be strongly proposed in different cardiovascular diseases as well as metabolic syndrome.

Melatonin-Induced Cytoskeleton Reorganization Leads to Inhibition of Melanoma Cancer Cell Proliferation.

Neuroindole melatonin, a hormone synthesized during the night mainly—but not exclusively—by the pineal gland of all vertebrates, functions as an adapting signal to the light-dark cycle. Its antioxidant, neuroprotective, anti-inflammatory, and antitumor properties are all well-known and widely reported. Melanoma is one of the most common carcinomas among developed countries and a type of tumor particularly difficult to fight back in medium/advanced stages. In contrast to other types of cancer, influence of melatonin on melanoma has been scarcely investigated. Thus, we have chosen the murine melanoma model B16-F10 cell line to study antiproliferative and antitumoral actions of melatonin. For this purpose, we combined both, cell culture and in vivo models. Melatonin reduced either, growth rate or migration of B16-F10 cells. Furthermore, melanin synthesis was altered by melatonin, promoting its synthesis. Melatonin also induced a G2/M cell cycle arrest and altered the cytoskeletal organization. To corroborate these results, we tested the effect of melatonin in the in vivo model of B16-F10 cell injection in the tail vein, which causes numerous lung metastases. Two different strategies of melatonin administration were used, namely, in drinking water, or daily intraperitoneal injection. However, contrary to what occurred in cell culture, no differences were observed between control and melatonin treated groups. Results obtained led us to conclude that melatonin exerts an antiproliferative and anti-migrating effect on this melanoma model by interfering with the cytoskeleton organization, but this pharmacological effect cannot be translated in vivo as the indole did not prevent metastasis in the murine model, suggesting that further insights into the effects of the indole in melanoma cells should be approached to understand this apparent paradox.