Melatonin-Induced Changes in Cytosolic Calcium Might be Responsible for Apoptosis Induction in Tumour Cells
Jazyk angličtina Země Německo Médium print-electronic
Typ dokumentu časopisecké články
PubMed
29169174
DOI
10.1159/000485290
PII: 000485290
Knihovny.cz E-zdroje
- Klíčová slova
- Apoptosis, Calcium, Cancer, ER-stress, Melatonin, Reactive oxygen species,
- MeSH
- apoptóza účinky léků MeSH
- cytosol metabolismus MeSH
- fluorescenční mikroskopie MeSH
- inositol-1,4,5-trisfosfát - receptory antagonisté a inhibitory genetika MeSH
- lidé MeSH
- malá interferující RNA metabolismus MeSH
- melatonin toxicita MeSH
- nádorové buněčné linie MeSH
- pumpa pro výměnu sodíku a vápníku antagonisté a inhibitory genetika metabolismus MeSH
- reaktivní formy kyslíku metabolismus MeSH
- RNA interference MeSH
- stres endoplazmatického retikula účinky léků MeSH
- transkripční faktor CHOP genetika metabolismus MeSH
- vápník metabolismus MeSH
- XBP1 genetika metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- inositol-1,4,5-trisfosfát - receptory MeSH
- malá interferující RNA MeSH
- melatonin MeSH
- pumpa pro výměnu sodíku a vápníku MeSH
- reaktivní formy kyslíku MeSH
- sodium-calcium exchanger 1 MeSH Prohlížeč
- transkripční faktor CHOP MeSH
- vápník MeSH
- Xbp1 protein, mouse MeSH Prohlížeč
- XBP1 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
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