Effect of Exogenous Melatonin on Morphological Features of B16 Melanoma in Mice

BACKGROUND: Constant illumination over a long period of time suppresses the hormone-synthesizing function of the pineal gland, leading to a decrease in melatonin levels and, consequently, to accelerated aging of the body, increased incidence of age-associated pathologies, including neoplasms, and shortened life expectancy. Melatonin has a pronounced antitumor effect. In particular, its antiproliferative effect is highlighted. Melanoma is one of the most malignant neoplasms in humans, originating from melanin-producing cells. In recent years, the proportion of older patients among patients with melanoma has been increasing, which makes it possible to classify this disease as age-associated. There is evidence that melatonin deficiency and the resulting disruption of the body’s circadian rhythms is one of the factors contributing to the development of melanoma.

AIM: To investigate the effect of exogenous melatonin on the morphological features of B16 melanoma in mice.

METHODS: The study was conducted on male hybrid mice of the BDF1 line (n = 60) at the age of 8 weeks, weighing 21–22 g. All animals received subcutaneous transplantation of B16/F10 melanoma in suspension. The mice were further divided into two groups, control and experimental. Animals of the experimental group were administered melatonin (Sigma, USA) at a dose of 5 mg/kg intragastrically from the first day of the study. On the 15th day after tumor transplantation, the tumor itself, as well as the lungs and liver, were removed. Pathomorphological examination of the tumor was performed, and the presence of lung and liver metastases was determined. Area of necrosis was measured on histological slides of the tumor stained with hematoxylin and eosin, and the nuclear-cytoplasmic ratio in tumor cells was calculated by measuring the cross-sectional area of nuclei and the cross-sectional area of cells. Graphing and statistical analysis of the results were performed using GraphPad Prism v8.41 (USA).

RESULTS: It was found that melatonin administration during the studied period reduced the mortality of mice with melanoma, decreased the incidence of tumor metastasis and tumor size. In addition, in melanomas of the experimental group of mice, signs of tumor regression in the form of foci of dystrophic and alterative changes were visualized, as well as a statistically significant increase in the area of tumor necrosis.

CONCLUSION: The present study showed that exogenous melatonin has a pronounced antitumor effect against B16 melanoma in mice. The obtained results allow planning more thorough and multidisciplinary studies for in-depth investigation of the mechanisms of melatonin antitumor effect.