Melatonin as antioxidant, geroprotector and anticarcinogen

Abstract

The effect of the pineal indole hormone melatonin on the life span of mice, rats and fruit flies has been studied using various approaches. It has been observed that in female CBA, SHR, SAM and transgenic HER-2/neu mice long-term administration of melatonin was followed by an increase in the mean life span. In rats, melatonin treatment increased survival of male and female rats. In D. melanogaster, supplementation of melatonin to nutrient medium during developmental stages produced contradictory results, but and increase in the longevity of fruit flies has been observed when melatonin was added to food throughout the life span. In mice and rats, melatonin is a potent antioxidant both in vitro and in vivo. Melatonin alone turned out neither toxic nor mutagenic in the Ames test and revealed clastogenic activity at high concentration in the COMET assay. Melatonin has inhibited mutagenesis and clastogenic effect of a number of indirect chemical mutagens. Melatonin inhibits the development of spontaneous and 7-12-dimethlbenz(a)anthracene (DMBA)- or N-nitrosomethylurea-induced mammary carcinogenesis in rodents; colon carcinogenesis induced by 1,2-dimethylhydrazine in rats, N-diethylnitrosamine-induced hepatocarcinogenesis in rats, DMBA-induced carcinogenesis of the uterine cervix and vagina in mice; benzo(a)pyrene-induced soft tissue carcinogenesis and lung carcinogenesis induced by urethan in mice. To identify molecular events regulated by melatonin, gene expression profiles were studied in the heart and brain of melatonin-treated CBA mice using cDNA gene expression arrays (15,247 and 16,897 cDNA clone sets, respectively). It was shown that genes controlling the cell cycle, cell/organism defense, protein expression and transport are the primary effectors for melatonin. Melatonin also increased the expression of some mitochondrial genes (16S, cytochrome c oxidases 1 and 3 (COX1 and COX3), and NADH dehydrogenases 1 and 4 (ND1 and ND4)), which agrees with its ability to inhibit free radical processes. Of great interest is the effect of melatonin upon the expression of a large number of genes related to calcium exchange, such as Cul5, Dcamkl1 and Kcnn4; a significant effect of melatonin on the expression of some oncogenesis-related genes was also detected. Thus, we believe that melatonin may be used for the prevention of premature aging and carcinogenesis.

Metformin extends life span of HER-2/neu transgenic mice and in combination with melatonin inhibits growth of transplantable tumors in vivo

“…8 In our experiments the treatment of transplantable HER2 mammary carcinoma and Ehrlich carcinoma with metformin with potent scavenger of ROS melatonin, 12,58 effectively inhibited the tumor growth. It was shown that melatonin suppressed expression HER2 in mammary adenocarcinomas in transgenic HER2/neu mice.…”

“…9 Treatment with melatonin inhibits development of mammary tumors in a number of another models both in vitro and in vivo. [10][11][12] In this paper, we for the first time present the results of study of effect of combined treatment with metformin and melatonin on some aging related biological parameters, on the survival and Population studies have shown that treatment with the antidiabetic biguanide metformin significantly reduced cancer risk. In our animal studies, metformin delayed the onset of mammary adenocarcinoma (MAC) in transgenic HeR-2/neu mice but not the onset of spontaneous mammary tumors in female SHR mice.…”

Melatonin and its use in atherosclerosis and dyslipidemia

“…42 Melatonin significantly influences gonadotrophin and sexual function in animals 43 and may possibly play a role during puberty (eg, hypogonadism in children with melatonin hypersecretion due to a pineal tumor), 44 although little is otherwise known. 45,46 Other properties of melatonin include a mild reduction in blood pressure, 47,48 and antioxidative 12,49,50 and anti-inflammatory 51,52 effects; the latter two are considered to influence cancer growth and life span, 53,54 and have a beneficial effect in several pathological conditions. 55 The absence of melatonin secretion is not a life-threatening state, in contrast with some other hormonal deficiencies.…”

Quantitative determination of melatonin in milk by LC-MS/MS

“…It controls many function in our daily life's especially sleepwake process, circadian rhythms. Melatonin is an excellent antioxidant, protective against many types of cancer (Anisimov et al 2006) and also contributes in communication of time of day to the infants through breast feed milk (Illnerova et al 1993). Melatonin has been used successfully for the treatment of jet-lag effects and other sleep disorder (James et al 1990;Jan and Espezel 1995).…”