Several papers have reported that calcium channel blocking drugs were associated with increased breast cancer risk and worsened prognosis. One of the most common signs of breast tumors is the presence of small deposits of calcium, known as microcalcifications. Therefore, we studied the effect of dihydropyridine nifedipine on selected calcium transport systems in MDA-MB-231 cells, originating from triple negative breast tumor and JIMT1 cells that represent a model of HER2-positive breast cancer, which possesses amplification of HER2 receptor, but cells do not response to HER2 inhibition treatment with trastuzumab. Also, we compared the effect of nifedipine on colorectal DLD1 and ovarian A2780 cancer cells. Both, inositol 1,4,5-trisphosphate receptor type 1 (IP3R1) and type 1 sodium calcium exchanger (NCX1) were upregulated due to nifedipine in DLD1 and A2780 cells, but not in breast cancer MDA-MB-231 and JIMT1 cells. On contrary to MDA-MB-231 and JIMT1 cells, in DLD1 and A2780 cells nifedipine induced apoptosis in a concentration-dependent manner. After NCX1 silencing and subsequent treatment with nifedipine, proliferation was decreased in MDA-MB-231, increased in DLD1 cells, and not changed in JIMT1 cells. Silencing of IP3R1 revealed increase in proliferation in DLD1 and JIMT1 cells, but caused decrease in proliferation in MDA-MB-231 cell line after nifedipine treatment. Interestingly, after nifedipine treatment migration was not significantly affected in any of tested cell lines after NCX1 silencing. Due to IP3R1 silencing, significant decrease in migration occurred in MDA-MB-231 cells after nifedipine treatment, but not in other tested cells. These results support different function of the NCX1 and IP3R1 in the invasiveness of various cancer cells due to nifedipine treatment.

• MeSH
• apoptóza účinky léků   genetika   MeSH
• blokátory kalciových kanálů farmakologie   MeSH
• inositol-1,4,5-trisfosfát - receptory genetika   metabolismus   MeSH
• kolorektální nádory genetika   metabolismus   patologie   MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• nádory prsu genetika   metabolismus   patologie   MeSH
• nádory vaječníků genetika   metabolismus   patologie   MeSH
• nifedipin farmakologie   MeSH
• pohyb buněk účinky léků   genetika   MeSH
• proliferace buněk účinky léků   genetika   MeSH
• protinádorové látky imunologicky aktivní farmakologie   MeSH
• pumpa pro výměnu sodíku a vápníku genetika   metabolismus   MeSH
• receptor erbB-2 genetika   metabolismus   MeSH
• regulace genové exprese u nádorů účinky léků   MeSH
• RNA interference MeSH
• trastuzumab farmakologie   MeSH
• triple-negativní karcinom prsu genetika   metabolismus   patologie   MeSH
• vápníková signalizace účinky léků   genetika   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The sodium/calcium exchanger (NCX) is a unique calcium transport system, generally transporting calcium ions out of the cell in exchange for sodium ions. Nevertheless, under special conditions this transporter can also work in a reverse mode, in which direction of the ion transport is inverted-calcium ions are transported inside the cell and sodium ions are transported out of the cell. To date, three isoforms of the NCX have been identified and characterized in humans. Majority of information about the NCX function comes from isoform 1 (NCX1). Although knowledge about NCX function has evolved rapidly in recent years, little is known about these transport systems in cancer cells. This review aims to summarize current knowledge about NCX functions in individual types of cancer cells.

• MeSH
• invazivní růst nádoru MeSH
• iontový transport MeSH
• lidé MeSH
• nádory metabolismus   MeSH
• pumpa pro výměnu sodíku a vápníku metabolismus   MeSH
• sodík metabolismus   MeSH
• vápník metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy 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.

• 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