Melatonin and cell death: differential actions on apoptosis in normal and cancer cells

Sainz, Rosa M.; Mayo, Juan C.; Rodríguez, Carmen; Tan, Dun Xian; López‐Burillo, Silvia; Reíter, Russel J.

doi:10.1007/s00018-003-2319-1

Cited by 275 publications

(241 citation statements)

References 161 publications

(145 reference statements)

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“…The observed opposite effects of melatonin in isolated mitochondria match previous observations of mitochondrial-mediated apoptosis in normal and cancer cells, as emphasized in a former review (Sainz et al 2003). A very recent paper reports that melatonin protects human leucocytes against MPT induction and apoptosis.…”

Section: Discussionsupporting

confidence: 86%

“…It has also been found that the indolamine induces mitochondrial-mediated apoptosis in human myeloid HL-60 cells (Bejarano et al 2009) but reduces this process in human leukocytes (Espino et al 2010). The differential actions exhibited by melatonin on mitochondria and apoptosis in normal and cancer cells were also previously reported in a review article (Sainz et al 2003).…”

Section: Introductionmentioning

confidence: 58%

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Interactions of melatonin with mammalian mitochondria. Reducer of energy capacity and amplifier of permeability transition

et al. 2011

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Melatonin, a metabolic product of the amino acid tryptophan, induces a dose-dependent energy drop correlated with a decrease in the oxidative phosphorylation process in isolated rat liver mitochondria. This effect involves a gradual decrease in the respiratory control index and significant alterations in the state 4/state 3 transition of membrane potential (DW). Melatonin, alone, does not affect the insulating properties of the inner membrane but, in the presence of supraphysiological Ca 2? , induces a DW drop and colloid-osmotic mitochondrial swelling. These events are sensitive to cyclosporin A and the inhibitors of Ca 2? transport, indicative of the induction or amplification of the mitochondrial permeability transition. This phenomenon is triggered by oxidative stress induced by melatonin and Ca 2? , with the generation of hydrogen peroxide and the consequent oxidation of sulfydryl groups, glutathione and pyridine nucleotides. In addition, melatonin, again in the presence of Ca 2? , can also induce substantial release of cytochrome C and AIF (apoptosis-inducing factor), thus revealing its potential as a pro-apoptotic agent.

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Section: Discussionsupporting

confidence: 86%

Section: Introductionmentioning

confidence: 58%

Interactions of melatonin with mammalian mitochondria. Reducer of energy capacity and amplifier of permeability transition

et al. 2011

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“…Studies in peripheral blood have suggested that melatonin inhibits apoptotic processes via its antioxidant properties [106], which is in line with many evidences showing that in some instances the apoptotic process occurs via oxidative signaling [107]. Alternative mechanisms have been proposed; in U937 monocytes, melatonin reduces apoptosis via intracellular signal transduction stimulated by interaction with MT1/MT2 plasma membrane receptors [23].…”

Section: Page 9 Of 29supporting

confidence: 55%

“…It has been long debated that melatonin in some instances may exert a pro-apoptotic role [106]; the mechanisms and rationale of this effect are unclear. However, upon Bcl-2 silencing, melatonin acquires pro-apoptotic abilities [108], indicating that the very finely regulated changes in Bcl-2 levels during lymphocyte maturation may confer different susceptibility to melatonin, modulating a pro-or anti-apoptotic effect according to the intracellular amount of Bcl-2.…”

Section: Page 12 Of 29mentioning

confidence: 99%

Melatonin: A pleiotropic molecule regulating inflammation

Radogna

Diederich

Ghibelli

2010

Biochemical Pharmacology

308

247

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Melatonin is a neurohormone produced by the pineal gland that regulates sleep and circadian functions. Melatonin also regulates inflammatory and immune processes acting as both an activator and inhibitor of these responses. Melatonin demonstrates endocrine, but also paracrine and autocrine effects in the leukocyte compartment: on one side, leukocytes respond to melatonin in a circadian fashion; on the other side, leukocytes are able to synthesize melatonin by themselves.With its endocrine and paracrine effects, melatonin differentially modulates pro-inflammatory enzymes, controls production of inflammatory mediators such as cytokines and leukotrienes and regulates the lifespan of leukocytes by interfering with apoptotic processes. Moreover, its potent anti-oxidant ability allows scavenging of oxidative stress in the inflamed tissues. The interesting timing of pro-and anti-inflammatory effects, such as those affecting lipoxygenase activity, suggests that melatonin might promote early phases of inflammation on one hand and contribute to its attenuation on the other hand, in order to avoid complications of chronic inflammation. This review aims at giving a comprehensive overview of the various inflammatory pathways regulated by this pleiotropic hormone.

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“…The effect of melatonin on the regulation of cellular apoptosis processes has also been documented (Sainz et al, 2003). Rodriguez-Osorio et al (2007) found a positive effect of melatonin on the total cell numbers per blastocyst, and this effect was attributed to its anti- Braz.…”

Section: Resultsmentioning

confidence: 94%

Melatonin in maturation media fails to improve oocyte maturation, embryo development rates and DNA damage of bovine embryos

Takada

Martins

Mingoti

et al. 2010

Sci. agric. (Piracicaba, Braz.)

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Melatonin (MEL) acts as a powerful scavenger of free radicals and direct gonadal responses to melatonin have been reported in the literature. Few studies, however, have evaluated the effect of MEL during in vitro maturation (IVM) on bovine embryos. This study tested the addition of MEL to maturation medium (MM) with no gonadotropins on nuclear maturation and embryo development rates and the incidence of DNA damage in resulting embryos. Cumulus-oocyte complexes were aspirated from abattoir ovaries and cultured in MM (TCM-199 medium supplemented with 10% fetal calf serum -FCS) at 39°C and 5% CO 2 in air. After 24 hours of culture in MM with 0.5 μg mL -1 FSH and 5.0 μg mL -1 LH; 10 -9 M MEL) or 10 -9 M MEL, 0.5 μg mL -1 FSH and 5.0 μg mL -1 LH, the oocytes were stained with Hoechst 33342 to evaluate nuclear maturation rate. After in vitro fertilization and embryo culture, development rates were evaluated and the blastocysts were assessed for DNA damage by Comet assay. There was no effect of melatonin added to the MM, alone or in combination with gonadotropins, on nuclear maturation, cleavage and blastocyst rates. These rates ranged between 88% to 90%, 85% to 88% and 42% to 46%, respectively. The extent of DNA damage in embryos was also not affected by MEL supplementation during IVM. The addition of 10 -9 M MEL to the MM failed to improve nuclear maturation and embryo development rates and the incidence of DNA damage in resulting embryos, but was able to properly substitute for gonadotropins during IVM. Key words: comet assay, embryos, gonadotropins, in vitro fertilization, melatonin Melatonina no meio de maturação não melhorou as taxas de maturação dos ovócitos, de desenvolvimento embrionário e a fragmentação do DNA dos embriões bovinos RESUMO: Melatonin (MEL) atua como um potente redutor de radicais livres. Efeito direto da MEL na função gonadal também foi observado. Existem poucos estudos relacionados ao efeito da MEL durante a maturação no desenvolvimento embrionário in vitro. Avaliou-se a adição de MEL no meio de maturação (sem gonadotrofinas) nas taxas de maturação nuclear e de desenvolvimento embrionário e na incidência de fragmentação do DNA nos embriões produzidos in vitro. Complexos cumulus-ovócitos foram aspirados de ovários provenientes de matadouros e cultivados em meio de maturação (Meio TCM-199 suplementado com 10% de soro fetal bovino) a 39°C e 5% CO 2 em ar. Após 24 horas de cultivo em meio de maturação com 0,5 μg mL -1 de FSH e 5,0 μg mL -1 de LH; 10 -9 M de MEL ou 10 -9 M de MEL, 0,5 μg mL -1 de FSH e 5,0 μg mL -1 de LH, os ovócitos foram corados com Hoechst 33342 para avaliação da taxa de maturação nuclear. A fragmentação do DNA dos blastocistos foi avaliada pela técnica do Cometa. Não houve efeito da MEL adicionada ao meio de maturação, com ou sem gonadotrofinas, nas taxas de maturação nuclear, clivagem e blastocistos. Os percentuais variaram entre 88% a 90%, 85% a 88% e 42% a 46%, respectivamente. O grau de fragmentação do DNA também não foi afetado pela adição de MEL ao meio de matur...

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Melatonin and cell death: differential actions on apoptosis in normal and cancer cells

Cited by 275 publications

References 161 publications

Interactions of melatonin with mammalian mitochondria. Reducer of energy capacity and amplifier of permeability transition

Interactions of melatonin with mammalian mitochondria. Reducer of energy capacity and amplifier of permeability transition

Melatonin: A pleiotropic molecule regulating inflammation

Melatonin in maturation media fails to improve oocyte maturation, embryo development rates and DNA damage of bovine embryos

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