Role of melatonin, melatonin receptors and STAT3 in the cardioprotective effect of chronic and moderate consumption of red wine

Lamont, Kim; Nduhirabandi, Frederic; Adam, Tasneem; Thomas, D. P.; Opie, Lionel H.; Lecour, Sandrine

doi:10.1016/j.bbrc.2015.08.064

Cited by 29 publications

(28 citation statements)

References 34 publications

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“…When measured in experimental studies, the severity of the long‐term neurobehavioral deficits associated with stroke have been also shown to be reduced when melatonin was given coincident with the IR episode . Many of the molecular details that are involved in melatonin's protective actions during IR have been elucidated in recent reports …”

Section: Melatonin As An Antioxidant: Waging War On Free Radicalsmentioning

confidence: 99%

“…222,223 Many of the molecular details that are involved in melatonin's protective actions during IR have been elucidated in recent reports. 190,[224][225][226][227] Herein, emphasis was placed on the neuroprotective and cardioprotective actions of melatonin that result from IR as hypoxia/reoxygenation in these organs often has dire consequences. These are, however, not the only organs where melatonin has preserved the morphological and functional integrity when they are subjected to IR.…”

Section: Melatonin As An Antioxidant: Evidence From Ischemia-reperfmentioning

confidence: 99%

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Melatonin as an antioxidant: under promises but over delivers

Reíter

Mayo

Tan

et al. 2016

Journal of Pineal Research

1,318

1,040

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Melatonin is uncommonly effective in reducing oxidative stress under a remarkably large number of circumstances. It achieves this action via a variety of means: direct detoxification of reactive oxygen and reactive nitrogen species and indirectly by stimulating antioxidant enzymes while suppressing the activity of pro-oxidant enzymes. In addition to these well-described actions, melatonin also reportedly chelates transition metals, which are involved in the Fenton/Haber-Weiss reactions; in doing so, melatonin reduces the formation of the devastatingly toxic hydroxyl radical resulting in the reduction of oxidative stress. Melatonin's ubiquitous but unequal intracellular distribution, including its high concentrations in mitochondria, likely aid in its capacity to resist oxidative stress and cellular apoptosis. There is credible evidence to suggest that melatonin should be classified as a mitochondria-targeted antioxidant. Melatonin's capacity to prevent oxidative damage and the associated physiological debilitation is well documented in numerous experimental ischemia/ reperfusion (hypoxia/reoxygenation) studies especially in the brain (stroke) and in the heart (heart attack). Melatonin, via its antiradical mechanisms, also reduces the toxicity of noxious prescription drugs and of methamphetamine, a drug of abuse.Experimental findings also indicate that melatonin renders treatment-resistant cancers sensitive to various therapeutic agents and may be useful, due to its multiple antioxidant actions, in especially delaying and perhaps treating a variety of agerelated diseases and dehumanizing conditions. Melatonin has been effectively used to combat oxidative stress, inflammation and cellular apoptosis and to restore tissue function in a number of human trials; its efficacy supports its more extensive use in a wider variety of human studies. The uncommonly high-safety profile of melatonin also bolsters this conclusion. It is the current feeling of the authors that, in view of the widely diverse beneficial functions that have been reported for melatonin, these may be merely epiphenomena of the more fundamental, yet-to-be identified basic action(s) of this ancient molecule. K E Y W O R D Sdiseases of aging, drug toxicity, free radicals, ischemia/reperfusion, mitochondria-targeted antioxidant, organ transplantation, statins

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Section: Melatonin As An Antioxidant: Waging War On Free Radicalsmentioning

confidence: 99%

Section: Melatonin As An Antioxidant: Evidence From Ischemia-reperfmentioning

confidence: 99%

Melatonin as an antioxidant: under promises but over delivers

Reíter

Mayo

Tan

et al. 2016

Journal of Pineal Research

1,318

1,040

View full text Add to dashboard Cite

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“…Indeed, overexpression of MT1 melatonin receptor enhanced anti-proliferative effect of melatonin in human breast cancer cells [51]. Also, MT is linked to the modulation of STAT3 [53,54] and inhibition of MT expression has been reported to down-regulate activation of STAT-3 [55]. In addition, melatonin has shown to inhibit tumorigenicity via STAT3 signaling [35].…”

Section: Discussionmentioning

confidence: 99%

Melatonin Synergizes with Sorafenib to Suppress Pancreatic Cancer via Melatonin Receptor and PDGFR-β/STAT3 Pathway

Fang¹,

Jung²,

Zhang³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignant tumors with poor prognosis. Conventional chemotherapies including gemcitabine have failed owing to weak response and side effects. Hence novel treatment regimens are urgently needed to improve the therapeutic efficacy. In this study, we aimed to assess the anticancer activity of melatonin and sorafenib as a novel therapy against PDAC. Methods: We used various apoptosis assay and PDAC xenograft model to assess anticancer effect in vitro and in vivo. We applied phospho-receptor tyrosine kinase (RTK) array and phospho-tyrosine kinase array to explore the mechanism of the combined therapy. Western blotting, proximity ligation assay, and immunoprecipitation assay were also performed for validation. Results: Melatonin synergized with sorafenib to suppress the growth of PDAC both in vitro and in vivo. The effect was due to increased apoptosis rate of PDAC cells that was accompanied by mitochondria dysfunction. The enhanced anticancer efficacy by the co-treatment could be explained by blockade of PDGFR-β/STAT3 signaling pathway and melatonin receptor (MT)-mediated STAT3. Conclusions: Melatonin reinforces the anticancer activity of sorafenib by downregulation of PDGFR-β/STAT3 signaling pathway and melatonin receptor (MT)-mediated STAT3. The combination of the two agents might be a potential therapeutic strategy for treating PDAC.

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“…In particular, TLR4 may trigger the activation of the SAFE pathway to promote cell survival following myocardial IRI [ 68 ]. Dietary melatonin, given at a concentration found in red wine, was demonstrated as respective trigger to confer cardioprotection [ 52 ] but also to prevent pulmonary hypertension via the activation of the SAFE pathway [ 59 ]. Based on the fact that high-density lipoproteins (HDL) can also activate the SAFE pathway, sphingosine-1 phosphate was identified as predominant component of HDL to protect against myocardial IRI [ 94 ], ultimately regulating the mitochondrial functions of cardiomyocytes [ 13 ].…”

Section: New Players In Cardiovascular Diseasesmentioning

confidence: 99%

From basic mechanisms to clinical applications in heart protection, new players in cardiovascular diseases and cardiac theranostics: meeting report from the third international symposium on “New frontiers in cardiovascular research”

et al. 2016

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In this meeting report, particularly addressing the topic of protection of the cardiovascular system from ischemia/reperfusion injury, highlights are presented that relate to conditioning strategies of the heart with respect to molecular mechanisms and outcome in patients’ cohorts, the influence of co-morbidities and medications, as well as the contribution of innate immune reactions in cardioprotection. Moreover, developmental or systems biology approaches bear great potential in systematically uncovering unexpected components involved in ischemia–reperfusion injury or heart regeneration. Based on the characterization of particular platelet integrins, mitochondrial redox-linked proteins, or lipid-diol compounds in cardiovascular diseases, their targeting by newly developed theranostics and technologies opens new avenues for diagnosis and therapy of myocardial infarction to improve the patients’ outcome.

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Role of melatonin, melatonin receptors and STAT3 in the cardioprotective effect of chronic and moderate consumption of red wine

Cited by 29 publications

References 34 publications

Melatonin as an antioxidant: under promises but over delivers

Melatonin as an antioxidant: under promises but over delivers

Melatonin Synergizes with Sorafenib to Suppress Pancreatic Cancer via Melatonin Receptor and PDGFR-β/STAT3 Pathway

From basic mechanisms to clinical applications in heart protection, new players in cardiovascular diseases and cardiac theranostics: meeting report from the third international symposium on “New frontiers in cardiovascular research”

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