Use of Melatonin in Cancer Treatment: Where Are We?

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(7), P. 3779 - 3779

Published: March 29, 2022

Cancer represents a large group of diseases accounting for nearly 10 million deaths each year. Various treatment strategies, including surgical resection combined with chemotherapy, radiotherapy, and immunotherapy, have been applied cancer treatment. However, the outcomes remain largely unsatisfying. Melatonin, as an endogenous hormone, is associated circadian rhythm moderation. Many physiological functions melatonin besides sleep–wake cycle control identified, such antioxidant, immunomodulation, anti-inflammation. In recent years, increasing number studies described anticancer effects melatonin. This has drawn our attention to potential usage in clinical setting, although huge obstacles still exist before its wide administration accepted. The exact mechanisms behind unclear, specific characters impede vivo investigation. this review, we will summarize latest advances studies, chemical properties, possible effects, ongoing trials. Importantly, challenges application be discussed, accompanied perspectives on future development. Finally, using proposed. present article provide comprehensive foundation applying preventive therapeutic agent

Language: Английский

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Revisiting the role of melatonin in human melanocyte physiology: A skin context perspective

Journal of Pineal Research, Journal Year: 2022, Volume and Issue: 72(3)

Published: Feb. 8, 2022

The evolutionarily ancient methoxyindoleamine, melatonin, has long perplexed investigators by its versatility of functions and mechanisms action, which include the regulation vertebrate pigmentation. Although first discovered through potent skin-lightening effects in amphibians, melatonin's role human skin hair follicle pigmentation impact on melanocyte physiology remain unclear. Synthesizing our limited current understanding this role, we specifically examine melanogenesis, oxidative biology, mitochondrial function, senescence, pigmentation-related clock gene activity, with emphasis skin, yet without ignoring instructive pointers from nonhuman species. Given strict dependence epithelial microenvironment, underscore that responses to melatonin are best interrogated a physiological tissue context. Current evidence suggests some metabolites inhibit both, melanogenesis (via reducing tyrosinase activity) proliferation stimulating membrane receptors (MT1, MT2). We discuss whether putative melanogenesis-inhibitory may occur via activation Nrf2-mediated PI3K/AKT signaling, estrogen receptor-mediated and/or melanocortin-1 receptor- cAMP-dependent melatonin-regulated changes peripheral genes regulate namely Bmal1 Per1. Melatonin also accumulate melanocytes where they exert net cyto- senescence-protective as well antioxidative operating free radical scavengers, synthesis activity ROS scavenging enzymes other antioxidants, promoting DNA repair, enhancing function. argue it is clinically biologically important definitively clarify cell culture-based observations translate into melatonin-induced pigmentary context, is, epidermis follicles ex vivo, confirmed clinical trial results. After defining major open questions field, close suggesting how begin answering them relevant, currently available preclinical situ research models.

Language: Английский

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Melatonin and cancer suppression: insights into its effects on DNA methylation

Cellular & Molecular Biology Letters, Journal Year: 2022, Volume and Issue: 27(1)

Published: Sept. 5, 2022

Abstract Melatonin is an important naturally occurring hormone in mammals. Melatonin-mediated biological effects include the regulation of circadian rhythms, which for optimal human health. Also, melatonin has a broad range immunoenhancing actions. Moreover, its oncostatic properties, especially regarding breast cancer, involve variety cancer-inhibitory processes and are well documented. Due to their promising on prognosis cancer patients, anti-cancer drugs with epigenetic actions have attracted significant amount attention recent years. Epigenetic modifications cancers categorized into three major including non-coding RNAs, histone modification, DNA methylation. Hence, modification latter event currently considered effective strategy treatment patients. Thereby, this report summarizes available evidence that investigated melatonin-induced altering status methylation different cells models, e.g., malignant glioma carcinoma. we discuss role artificial light at night (ALAN)-mediated inhibitory secretion subsequent impact global cells.

Language: Английский

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The potential influence of melatonin on mitochondrial quality control: a review

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 11, 2024

Mitochondria are critical for cellular energetic metabolism, intracellular signaling orchestration and programmed death regulation. Therefore, mitochondrial dysfunction is associated with various pathogeneses. The maintenance of homeostasis functional recovery after injury coordinated by biogenesis, dynamics autophagy, which collectively referred to as quality control. There increasing evidence that mitochondria important targets melatonin exert protective effects under pathological conditions. Melatonin, an evolutionarily conserved tryptophan metabolite, can be synthesized, transported metabolized in mitochondria. In this review, we summarize the role damaged elimination energy supply regulating control, may provide new strategies clinical treatment mitochondria-related diseases.

Language: Английский

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Melatonin, Melatonin Receptors and Sleep: Moving Beyond Traditional Views

Journal of Pineal Research, Journal Year: 2024, Volume and Issue: 76(7)

Published: Oct. 1, 2024

ABSTRACT Sleep, constituting approximately one‐third of the human lifespan, is a crucial physiological process essential for physical and mental well‐being. Normal sleep consists an orderly progression through wakefulness, non‐rapid eye movement (NREM) sleep, rapid (REM) all which are tightly regulated. Melatonin, often referred to as “hormone sleep,” plays pivotal role regulator sleep/wake cycle exerts its effects high‐affinity G‐protein coupled receptors known MT1 MT2. Selective modulation these presents promising therapeutic avenue disorders. This review examines research on multifaceted melatonin in regulation, focusing selective ligands targeting MT2 receptors, well studies involving knockout mice. Contrary common beliefs, growing evidence suggests that melatonin, might not only influence circadian aspects but likely, also modulate homeostatic architecture, or could be molecule linking regulation sleep. Furthermore, distinct brain localization with primarily regulating REM NREM discussed. Collectively, extends beyond circulating levels peak melatonin; it critically involves expression, molecular activation, regulatory functions across various regions nuclei involved underscores importance ongoing investigation into roles Such efforts expected pave way development targeted ligands, thereby optimizing interventions

Language: Английский

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Melatonin and ferroptosis: Mechanisms and therapeutic implications

Biochemical Pharmacology, Journal Year: 2023, Volume and Issue: 218, P. 115909 - 115909

Published: Nov. 4, 2023

Language: Английский

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Melatonin as a potential treatment for septic cardiomyopathy

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 166, P. 115305 - 115305

Published: Aug. 22, 2023

Septic cardiomyopathy (SCM) is a common complication of sepsis contributing to high mortality rates. Its pathophysiology involves complex factors, including inflammatory cytokines, mitochondrial dysfunction, oxidative stress, and immune dysregulation. Despite extensive research, no effective pharmacological agent has been established for sepsis-induced cardiomyopathy. Melatonin, hormone with diverse functions in the body, emerged as potential SCM through its anti-oxidant, anti-inflammatory, anti-apoptotic, cardioprotective roles. Through various molecular levels mechanism action, it counterattacks adverse event sepsis. Experimental studies have mentioned that melatonin protects against many cardiovascular diseases exerts preventive effects on SCM. Moreover, investigated combination other drugs such antibiotics, resveratrol, anti-oxidants showing synergistic reducing inflammation, improving cardiac function. While preclinical demonstrated positive results, clinical trials are required establish optimal dosage, route administration, treatment duration safety profile, low toxicity, natural occurrence human body provide favorable basis use. This review aims an overview current evidence use (SICM). Melatonin appears be promising possible demands further investigation.

Language: Английский

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Post-traumatic stress disorder, dyssomnias, and metabolic syndrome

INTERNATIONAL JOURNAL OF ENDOCRINOLOGY (Ukraine), Journal Year: 2024, Volume and Issue: 20(1), P. 58 - 67

Published: March 3, 2024

Post-traumatic stress disorder (PTSD) and metabolic syndrome (MetS) frequently coexist share neurobiological clinical features. In particular, the results of meta-analyses indicate a higher prevalence MetS in patients with PTSD compared to general population. is also recognized risk factor for MetS. This synchronicity can be partially explained by pathogenetic pathways present both conditions. These include genetic factors, dysfunction hypothalamic-pituitary-adrenal axis, chronic low-grade inflammation, oxidative stress, insulin resistance, immune dysregulation. Thus, similar mechanisms are involved worsening development adverse cardiovascular events associated Dyssomnias one characteristic features PTSD. Today, it believed that posttraumatic circadian rhythm disorders core not secondary feature PTSD, which mediate correlates due homeostasis imbalance. At same time, dyssomnias, chronodestruction, depressive part pathogenesis obesity, treatment dyssomnias key tasks prevention comorbid Regulation sleep processes rhythms through exogenous intervention, especially melatonergic drugs, likely preventing treating people who have The purpose this review analyze specifics relationships between MetS, disorders. We conducted search Scopus, Science Direct (from Elsevier), PubMed, including Medline databases. words used were “post-traumatic disorder,” “dyssomnias,” “chronodestruction,” “metabolic syndrome”. identification research findings found during online searches manual searching bibliography publications.

Language: Английский

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Melatonin Use during Pregnancy and Lactation Complicated by Oxidative Stress: Focus on Offspring’s Cardiovascular–Kidney–Metabolic Health in Animal Models

Antioxidants, Journal Year: 2024, Volume and Issue: 13(2), P. 226 - 226

Published: Feb. 12, 2024

Cardiovascular-kidney-metabolic (CKM) syndrome has emerged as a major global public health concern, posing substantial threat to human health. Early-life exposure oxidative stress may heighten vulnerability the developmental programming of adult diseases, encompassing various aspects CKM syndrome. Conversely, initiation adverse processes can potentially be thwarted through early-life antioxidant interventions. Melatonin, originally recognized for its properties, is an endogenous hormone with diverse biological functions. While melatonin demonstrated benefits in addressing disorders linked stress, there been comparatively less focus on investigating reprogramming effects This review consolidates current knowledge role during pregnancy and lactation inducing traits offspring, emphasizing underlying mechanisms. The multifaceted regulating mediating fetal programming, preventing outcomes offspring positions it promising strategy. Currently, lack sufficient information humans, available evidence primarily originates from animal studies. opens up new avenues novel preventive intervention

Language: Английский

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Cardiac-targeted delivery of nuclear receptor RORα via ultrasound targeted microbubble destruction optimizes the benefits of regular dose of melatonin on sepsis-induced cardiomyopathy

Biomaterials Research, Journal Year: 2023, Volume and Issue: 27(1)

Published: Feb. 9, 2023

Large-dose melatonin treatment in animal experiments was hardly translated into humans, which may explain the dilemma that protective effects against myocardial injury have been challenged by clinical trials. Ultrasound-targeted microbubble destruction (UTMD) has considered a promising drug and gene delivery system to target tissue. We aim investigate whether cardiac of receptor mediated UTMD technology optimizes efficacy clinically equivalent dose sepsis-induced cardiomyopathy.Melatonin receptors patients rat models with lipopolysaccharide (LPS)- or cecal ligation puncture (CLP)-induced sepsis were assessed. Rats received UTMD-mediated RORα/cationic microbubbles (CMBs) at 1, 3 5 days before CLP surgery. Echocardiography, histopathology oxylipin metabolomics assessed 16-20 h after inducing fatal sepsis.We observed lower serum than healthy controls, blood hearts Sprague-Dawley LPS- CLP-induced sepsis. Notably, mild (2.5 mg/kg) intravenous did not substantially improve septic cardiomyopathy. found decreased nuclear RORα, MT1/2, under lethal weaken potential benefits treatment. In vivo, repeated RORα/CMBs exhibited favorable biosafety, efficiency specificity, significantly strengthening safe on heart dysfunction rats. The RORα improved mitochondrial profiles, although there no significant influence systemic inflammation.These findings provide new insights suboptimal effect use clinic solutions overcome challenges. be promisingly interdisciplinary pattern

Language: Английский

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