An updated review of mechanistic potentials of melatonin against cancer: pivotal roles in angiogenesis, apoptosis, autophagy, endoplasmic reticulum stress and oxidative stress

Mehrzadi, Saeed; Pourhanifeh, Mohammad Hossein; Mirzaei, Alireza; Moradian, Farid; Hosseinzadeh, Azam

doi:10.1186/s12935-021-01892-1

Cited by 50 publications

(37 citation statements)

References 202 publications

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“…MLT is an active hormone secreted by the conarium and has antioxidant stress and anti-inflammatory functions ( Reiter et al, 2014 ; Reiter et al, 2017 ; Amaral and Cipolla-Neto 2018 ; Cipolla-Neto and Amaral 2018 ; Hardeland 2018 ). Based on previous research, MLT protects against ischemia-reperfusion and cancer, which are closely related to improving angiogenesis and suppressing apoptosis ( Yeung et al, 2015 ; Sun et al, 2016 ; Gou et al, 2020 ; Mehrzadi et al, 2021 ). However, it is unclear what effect MLT has on multi-territory perforator flaps.…”

Section: Discussionmentioning

confidence: 99%

Melatonin Improved the Survival of Multi-Territory Perforator Flaps by Promoting Angiogenesis and Inhibiting Apoptosis via the NRF2/FUNDC1 Axis

et al. 2022

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Background: Multi-territory perforator flaps are a reconstructive measure for repairing large soft tissue defects caused by tumors or trauma. However, the use of these flaps in clinical practice has been restricted due to the uncertain blood supply. Therefore, promoting the survival of the multi-territory perforator flap is critical for clinical repair and reconstruction. In our study, we explored the effects of melatonin (MLT) on multi-territory perforator flaps and the possible molecular mechanisms.Materials and Methods: Seventy-two Sprague–Dawley rats (250–300 g) were randomly divided into 3 groups (n = 24): Control, MLT and MLT + ML385 groups. First, we assessed the survival area of the flap, followed by the micro-vessel density and CD31-positive vessel expression. Apoptosis of the skin flap under immunofluorescence and expression of the apoptosis-related proteins Bcl-2, Bax and Caspase3 were measured. Additionally, angiogenesis of the skin flaps was shown by angiography, and NRF2 and FUNDC1 mRNA and protein expression was detected by real-time PCR and western blotting.Results: The results showed that MLT increased the survival area of the multi-territory perforator flap, which was related to increased angiogenesis and decreased apoptosis. We also found that mRNA and protein of NRF2 and FUNDC1 levels were significantly increased after MLT treatment, and an NRF2 inhibitor reversed the ability of MLT to enhance multi-territory perforator flap survival, promote angiogenesis and inhibit apoptosis and reduced FUNDC1 protein expression.Conclusion: MLT promoted angiogenesis and inhibited apoptosis to promote the survival of multi-territory perforator flaps, which may be regulated via the NRF2/FUNDC1 axis.

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Section: Discussionmentioning

confidence: 99%

Melatonin Improved the Survival of Multi-Territory Perforator Flaps by Promoting Angiogenesis and Inhibiting Apoptosis via the NRF2/FUNDC1 Axis

et al. 2022

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“…Melatonin has been proven as an ideal anticancer agent in various cancers 29‐32 . Studying melatonergic regulators in cancer is necessary to understand tumorigenesis and to explore potential targets for clinical treatment.…”

Section: Discussionmentioning

confidence: 99%

Pan‐cancer analyses reveal genomics and clinical characteristics of the melatonergic regulators in cancer

Zhang

Jiang

et al. 2021

Journal of Pineal Research

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Melatonin, an endogenous hormone, plays protective roles in cancer. In addition to regulating circadian rhythms, sleep, and neuroendocrine activity, melatonin functions in various survival pathways. However, the mechanisms of melatonin regulation in cancer remain unknown. In the present study, we performed a comprehensive characterization of melatonin regulators in 9125 tumor samples across 33 cancer types using multi‐omic data from The Cancer Genome Atlas and Cancer Cell Line Encyclopedia. In the genomic landscape, we identified the heterozygous amplification of AANAT and GPR50, and heterozygous deletion of PER3, CYP2C19, and MTNR1A as the dominant alteration events. Expression analysis revealed methylation‐mediated downregulation of melatonergic regulator expression. In addition, we found that melatonergic regulator expression could be used to predict patient survival in various cancers. In depth, microRNA (miRNA) analysis revealed an miRNA‐mRNA interaction network, and the deregulated miRNAs were involved in melatonin secretion and metabolism by targeting circadian clock genes. Pathway analysis showed that melatonergic regulators were associated with inhibition of apoptosis, the cell cycle, the DNA damage response, and activation of RAS/MAPK and RTK signaling pathways. Importantly, by mining the Genomics of Drug Sensitivity in Cancer database, we discovered a number of potential drugs that might target melatonergic regulators. In summary, this study revealed the genomic alteration and clinical characteristics of melatonergic regulators across 33 cancers, which might clarify the relationship between melatonin and tumorigenesis. Our findings also might provide a novel approach for the clinical treatment of cancers.

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“…Melatonin receptor suppresses ER-α-mediated transcriptional activity in ER-α-positive breast tumor cells. The arrest of cell cycle and the cell proliferation are mediated by the inhibitory actions on Ca 2+ signaling and CaM expression [25], stimulation of p53 expression [45], and p21-gene transcription (Figure 2) [46]. It was reported that blocking of MT1/MT2 receptors in MCF-7 cells showed impaired p53-mediated repairing of DNA damage [47].…”

Section: Anti-proliferative Effects Of Melatonin On Breast Cancer Cellsmentioning

confidence: 97%

The potential anti-cancer effects of melatonin on breast cancer

Das

Samanta

2022

Exploration of Medicine

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Melatonin is the primary hormone of the pineal gland that is secreted at night. It regulates many physiological functions, including the sleep-wake cycle, gonadal activity, free radical scavenging, immunomodulation, neuro-protection, and cancer progression. The precise functions of melatonin are mediated by guanosine triphosphate (GTP)-binding protein (G-protein) coupled melatonin receptor 1 (MT1) and MT2 receptors. However, nuclear receptors are also associated with melatonin activity. Circadian rhythm disruption, shift work, and light exposure at night hamper melatonin production. Impaired melatonin level promotes various pathophysiological changes, including cancer. In our modern society, breast cancer is a serious problem throughout the world. Several studies have been indicated the link between low levels of melatonin and breast cancer development. Melatonin has oncostatic properties in breast cancer cells. This indolamine advances apoptosis, which arrests the cell cycle and regulates metabolic activity. Moreover, melatonin increases the treatment efficacy of cancer and can be used as an adjuvant with chemotherapeutic agents.

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An updated review of mechanistic potentials of melatonin against cancer: pivotal roles in angiogenesis, apoptosis, autophagy, endoplasmic reticulum stress and oxidative stress

Cited by 50 publications

References 202 publications

Melatonin Improved the Survival of Multi-Territory Perforator Flaps by Promoting Angiogenesis and Inhibiting Apoptosis via the NRF2/FUNDC1 Axis

Melatonin Improved the Survival of Multi-Territory Perforator Flaps by Promoting Angiogenesis and Inhibiting Apoptosis via the NRF2/FUNDC1 Axis

Pan‐cancer analyses reveal genomics and clinical characteristics of the melatonergic regulators in cancer

The potential anti-cancer effects of melatonin on breast cancer

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