Dose-dependent effect of melatonin on life span and spontaneous tumor incidence in female SHR mice

Anisimov, Vladimir N.; Alimova, Irina; Baturin, Dmitri A.; Popovich, Irina G.; Zabezhinski, Mark A.; Rosenfeld, Svetlana V; Mantón, Kenneth G.; Semenchenko, Anna V.; Yashin, Anatoli I.

doi:10.1016/s0531-5565(02)00240-1

Cited by 48 publications

(22 citation statements)

References 48 publications

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“…Melatonin was used at a dose that has proved effective for life span extension and anti-carcinogenic effect. 5,10,60 Melatonin was dissolved in several drops of 96% on the survival and the life span are different in the previous experiment 5 and in present study, whereas the patterns of the drug effect on development of mammary carcinomas very similar and practically identical. However, it is difficult to exclude finally that calorie restriction, metformin and rapamycin may delay cancer by indirect mechanism, slowing age-related processes.…”

Section: Discussioncontrasting

confidence: 53%

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

Anisimov

Egormin²,

Piskunova³

et al. 2010

Cell Cycle

163

100

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Section: Discussioncontrasting

confidence: 53%

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

Anisimov

Egormin²,

Piskunova³

et al. 2010

Cell Cycle

163

100

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“…Finally, because melatonin is a potent free radical scavenger, its deficiency may result in reduced antioxidant protection in the elderly which may have significance not only for aging per se but also may contribute to the incidence or severity of some agerelated diseases (Karasek 2004). Functionally, melatonin has been linked to the regulation of seasonal reproduction (Reiter 1980;Pang et al 1998), strengthening of circadian rhythms (Ardelt 1989), stimulation of the immune system (Guerrero and Reiter 2002;Maestroni 2001), inhibition of cancer initiation (Karbownik and Reiter 2002), tumour growth (Sauer et al 2001;Vladimir et al 2003), sleep processes (Dijk and Cajochen 1997), and the potential for use in photodynamic therapy in the destruction of tumors (Perotti et al 2002;Maharaj et al 2005a). That melatonin functions as a powerful free radical scavenger and antioxidant was only uncovered in the last decade (Tan et al 1993a;Hardeland et al 1995;Reiter et al 2002).…”

Section: Introductionmentioning

confidence: 99%

Melatonin: New Places in Therapy

2007

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The fact that the full extent of the function of the pineal gland has not yet been elucidated, has stimulated melatonin research worldwide. This review introduces melatonin's mechanism of action, direct and indirect antioxidant actions as well as the antioxidant properties of its metabolites, 6-hydroxymelatonin (6-OHM) and N-acetyl-N-formyl-5-methoxykynurenamine (AFMK). At present the mechanism of action is proposed to be receptor-, protein- and nonprotein-mediated. From its popular role in the treatment of jetlag, melatonin is now implicated in the reduction of oxidative stess, both as a free radical scavenger and antioxidant. Melatonin's direct scavenging action in respect of the following will be discussed: superoxide anions, hydrogen peroxide, hydroxyl radicals, singlet oxygen, peroxy radicals and nitric oxide/peroxy nitrite anions. In addition melatonin also possesses indirect antioxidant activity and the role of its metabolites, AFMK and 6-OHM will be presented. It is these free radical scavenging and antioxidant properties of melatonin that has shifted the focus from that of merely strengthening circadian rhythms to that of neuroprotectant: a new place in therapy.

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“…Treatment with melatonin was followed by a 4.3-fold increase in malignant tumor incidence in comparison with that of the control (Table 1). In a recent experiment conducted in our laboratory, melatonin (2 mg/L or 20 mg/L) was given with drinking water for 5 consecutive days every month to female Swiss-derived SHR mice starting at the age of 3 months (15). There were 50 mice in each group.…”

Section: Introductionmentioning

confidence: 99%

Effects of Exogenous Melatonin—A Review

Anisimov

2003

Toxicol Pathol

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The results of studies on the effect of pineal indole hormone melatonin on the life span of mice, rats, fruit flies, and worms are critically reviewed. In mice, long-term administration of melatonin was followed by an increase in their life span in 12 experiments and had no effect in 8 of 20 different experiments. In D. melanogaster, the supplementation of melatonin to the nutrient medium during developmental stages gave contradictory results, but when melatonin was added to food throughout the life span, an increase in the longevity of fruit flies has been observed. Melatonin decreased the survival of C. elegans but increased the clonal life span of planaria Paramecium tertaurelia. Available data suggest antioxidant and atherogenic effects of melatonin. Melatonin alone turned out to be neither toxic nor mutagenic in the Ames test and revealed clastogenic activity in high concentration in the COMET assay. Melatonin inhibits mutagenesis induced by irradiation and by indirect chemical mutagens and inhibits the development of spontaneous and chemical-induced tumors in mice and rats. Further studies and clinical trials are needed to verify that melatonin is both safe and has geroprotector efficacy for humans.

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Dose-dependent effect of melatonin on life span and spontaneous tumor incidence in female SHR mice

Cited by 48 publications

References 48 publications

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

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

Melatonin: New Places in Therapy

Effects of Exogenous Melatonin—A Review

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