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Melatonin-Induced Changes in Cytosolic Calcium Might be Responsible for Apoptosis Induction in Tumour Cells
B. Chovancova, S. Hudecova, L. Lencesova, P. Babula, I. Rezuchova, A. Penesova, M. Grman, R. Moravcik, M. Zeman, O. Krizanova,
Language English Country Switzerland
Document type Journal Article
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from 2013-01-01 to 2018-12-31
PubMed
29169174
DOI
10.1159/000485290
Knihovny.cz E-resources
- MeSH
- Apoptosis drug effects MeSH
- Cytosol metabolism MeSH
- Microscopy, Fluorescence MeSH
- Inositol 1,4,5-Trisphosphate Receptors antagonists & inhibitors genetics MeSH
- Humans MeSH
- RNA, Small Interfering metabolism MeSH
- Melatonin toxicity MeSH
- Cell Line, Tumor MeSH
- Sodium-Calcium Exchanger antagonists & inhibitors genetics metabolism MeSH
- Reactive Oxygen Species metabolism MeSH
- RNA Interference MeSH
- Endoplasmic Reticulum Stress drug effects MeSH
- Transcription Factor CHOP genetics metabolism MeSH
- Calcium metabolism MeSH
- X-Box Binding Protein 1 genetics metabolism MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
BACKGROUND/AIMS: Melatonin is a hormone transferring information about duration of darkness to the organism and is known to modulate several signaling pathways in the cells, e.g. generation of endoplasmic reticulum stress, oxidative status of the cells, etc. Melatonin has been shown to exert antiproliferative and cytotoxic effects on various human cancers. We proposed that this hormone can differently affect tumour cells and healthy cells. METHODS: We compared the effect of 24 h melatonin treatment on calcium transport (by fluorescent probes FLUO-3AM and Rhod-5N), ER stress (determined as changes in the expression of CHOP, XBP1 and fluorescently, using Thioflavin T), ROS formation (by CellROX® Green/Orange Reagent) and apoptosis induction (by Annexin-V-FLUOS/propidiumiodide) in two tumour cell lines - ovarian cancer cell line A2780 and stable cell line DLD1 derived from colorectal carcinoma, with non-tumour endothelial cell line EA.hy926. RESULTS: Melatonin increased apoptosis in both tumour cell lines more than twice, while in EA.hy926 cells the apoptosis was increased only by 30%. As determined by silencing with appropriate siRNAs, both, type 1 sodium/calcium exchanger and type 1 IP3 receptor are involved in the apoptosis induction. Antioxidant properties of melatonin were significantly increased in EA.hy926 cells, while in tumour cell lines this effect was much weaker. CONCLUSION: Taken together, melatonin has different antioxidative effects on tumour cells compared to non-tumour ones; it also differs in the ability to induce apoptosis through the type 1 sodium/calcium exchanger, and type 1 IP3 receptor. Different targeting of calcium transport systems in tumour and normal, non-tumour cells is suggested as a key mechanism how melatonin can exert its anticancer effects. Therefore, it might have a potential as a novel therapeutic implication in cancer treatment.
Department of Physiology Faculty of Medicine Masaryk University Brno Czech Republic
Institute of Virology Biomedical Research Center Slovak Academy of Sciences Bratislava Slovakia
References provided by Crossref.org
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