Ultrastructural aspects of melatonin cytotoxicity on Caco-2 cells in vitro

Batista, Ana Paula Castor; Silva, Terezinha G. da; Teixeira, Álvaro Aguiar Coelho; Medeiros, Paloma Lys de; Teixeira, Valéria Wanderley; Alves, Luíz Carlos; Santos, Fábio André Brayner dos; Silva, Eliete C.

doi:10.1016/j.micron.2013.12.003

Cited by 26 publications

(18 citation statements)

References 40 publications

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“…Based on these considerations, 50-1 µmol/L melatonin concentrations were selected to evaluate the effects of melatonin dosages compatible with those reachable in the lumen gut after the intake of dietary supplements, while concentrations between 100 and 1 nmol/L were chosen to evaluate the effect of the physiological concentrations in the GIT. Batista et al 35 demonstrated the cytotoxicity effects of melatonin at concentration in the 1-5 μmol/L range on proliferating Caco-2 cells. 35 In the same cellular model, higher melatonin concentrations, up to 200 μmol/L, did not show any effect.…”

Section: Resultsmentioning

confidence: 99%

“…Batista et al 35 demonstrated the cytotoxicity effects of melatonin at concentration in the 1-5 μmol/L range on proliferating Caco-2 cells. 35 In the same cellular model, higher melatonin concentrations, up to 200 μmol/L, did not show any effect. In our experimental conditions, Caco-2 cells are terminally differentiated after 21-days from cell seeding, and in contraposition to Batista's work, they are not proliferating cells.…”

Section: Resultsmentioning

confidence: 99%

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Melatonin reduces inflammatory response in human intestinal epithelial cells stimulated by interleukin‐1β

Mannino

Caradonna

Cruciata

et al. 2019

Journal of Pineal Research

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Melatonin is the main secretory product of the pineal gland, and it is involved in the regulation of periodic events. A melatonin production independent of the photoperiod is typical of the gut. However, the local physiological role of melatonin at the intestinal tract is poorly characterized. In this study, we evaluated the anti‐inflammatory activities of melatonin in an in vitro model of inflamed intestinal epithelium. To this purpose, we assessed different parameters usually associated with intestinal inflammation using IL‐1β‐stimulated Caco‐2 cells. Differentiated monolayers of Caco‐2 cells were preincubated with melatonin (1 nmol/L‐50 μmol/L) and then exposed to IL‐1β. After each treatment, different inflammatory mediators, DNA‐breakage, and global DNA methylation status were assayed. To evaluate the involvement of melatonin membrane receptors, we also exposed differentiated monolayers to melatonin in the presence of luzindole, a MT1 and MT2 antagonist. Our results showed that melatonin, at concentrations similar to those obtained in the lumen gut after ingestion of dietary supplements for the treatment of sleep disorders, was able to attenuate the inflammatory response induced by IL‐1β. Anti‐inflammatory effects were expressed as both a decrease of the levels of inflammatory mediators, including IL‐6, IL‐8, COX‐2, and NO, and a reduced increase in paracellular permeability. Moreover, the protection was associated with a reduced NF‐κB activation and a prevention of DNA demethylation. Conversely, luzindole did not reverse the melatonin inhibition of stimulated‐IL‐6 release. In conclusion, our findings suggest that melatonin, through a local action, can modulate inflammatory processes at the intestinal level, offering new opportunities for a multimodal management of IBD.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Melatonin reduces inflammatory response in human intestinal epithelial cells stimulated by interleukin‐1β

Mannino

Caradonna

Cruciata

et al. 2019

Journal of Pineal Research

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“…Another study investigated the ultrastructural aspect of melatonin cytotoxicity on Caco-2 human colon adenocarcinoma cell line. Results showed that ultrastructurally, Caco-2 cells showed morphological changes in melatonin treatments at 1.56 and 0.78 μg/mL with characteristics of cell degeneration as shown by the absence of microvilli, mitochondrial degeneration, presence of numerous vacuoles, and nuclear fragmentation, indicating that melatonin could promote cytotoxicity in Caco-2 cells [169]. Furthermore, a study determined the interaction between cell death and cellular senescence in human colorectal cancer cells induced by melatonin [170].…”

Section: Experimental Studiesmentioning

confidence: 99%

Melatonin for the prevention and treatment of cancer

et al. 2017

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The epidemiological studies have indicated a possible oncostatic property of melatonin on different types of tumors. Besides, experimental studies have documented that melatonin could exert growth inhibition on some human tumor cells in vitro and in animal models. The underlying mechanisms include antioxidant activity, modulation of melatonin receptors MT1 and MT2, stimulation of apoptosis, regulation of pro-survival signaling and tumor metabolism, inhibition on angiogenesis, metastasis, and induction of epigenetic alteration. Melatonin could also be utilized as adjuvant of cancer therapies, through reinforcing the therapeutic effects and reducing the side effects of chemotherapies or radiation. Melatonin could be an excellent candidate for the prevention and treatment of several cancers, such as breast cancer, prostate cancer, gastric cancer and colorectal cancer. This review summarized the anticancer efficacy of melatonin, based on the results of epidemiological,experimental and clinical studies, and special attention was paid to the mechanisms of action.

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“…Another route of action by which melatonin initiates tumor cytotoxicity is the induction of morphological damage in CRC cells. When human Caco‐2 cells were exposed for 24 hours to 0.78‐50 µg melatonin/mL, DNA fragmentation, mitochondrial degeneration, and cellular vacuolization were observed; these are clear signs of a cellular degeneration most likely related to the enhancement of ROS . Melatonin and its recently found plant‐derivative 2‐hydroxymelatonin, have proven inhibitory actions on some proliferating human CRC cells .…”

Section: Multimodal Approach Using Melatonin Against Progression and mentioning

confidence: 99%

The emergence of melatonin in oncology: Focus on colorectal cancer

Gil‐Martín

Egea

Reíter

et al. 2019

Medicinal Research Reviews

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Within the last few decades, melatonin has increasingly emerged in clinical oncology as a naturally occurring bioactive molecule with substantial anticancer properties and a pharmacological profile optimal for joining the currently available pharmacopeia. In addition, extensive experimental data shows that this chronobiotic agent exerts oncostatic effects throughout all stages of tumor growth, from initial cell transformation to mitigation of malignant progression and metastasis; additionally, melatonin alleviates the side effects and improves the welfare of radio/chemotherapy‐treated patients. Thus, the support of clinicians and oncologists for the use of melatonin in both the treatment and proactive prevention of cancer is gaining strength. Because of its epidemiological importance and symptomatic debut in advanced stages of difficult clinical management, colorectal cancer (CRC) is a preferential target for testing new therapies. In this regard, the development of effective forms of clinical intervention for the improvement of CRC outcome, specifically metastatic CRC, is urgent. At the same time, the need to reduce the costs of conventional anti‐CRC therapy results is also imperative. In light of this status quo, the therapeutic potential of melatonin, and the direct and indirect critical processes of CRC malignancy it modulates, have aroused much interest. To illuminate the imminent future on CRC research, we focused our attention on the molecular mechanisms underlying the multiple oncostatic actions displayed by melatonin in the onset and evolution of CRC and summarized epidemiological evidence, as well as in vitro, in vivo and clinical findings that support the broadly protective potential demonstrated by melatonin.

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Ultrastructural aspects of melatonin cytotoxicity on Caco-2 cells in vitro

Cited by 26 publications

References 40 publications

Melatonin reduces inflammatory response in human intestinal epithelial cells stimulated by interleukin‐1β

Melatonin reduces inflammatory response in human intestinal epithelial cells stimulated by interleukin‐1β

Melatonin for the prevention and treatment of cancer

The emergence of melatonin in oncology: Focus on colorectal cancer

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