Calcium signaling affects migration and proliferation differently in individual cancer cells due to nifedipine treatment
Language English Country England, Great Britain Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
31706846
DOI
10.1016/j.bcp.2019.113695
PII: S0006-2952(19)30394-6
Knihovny.cz E-resources
- Keywords
- Apoptosis, Breast cancer, Inositol 1,4,5-trisphosphate receptor, Migration, Sodium calcium exchanger 1,
- MeSH
- Apoptosis drug effects genetics MeSH
- Calcium Channel Blockers pharmacology MeSH
- Inositol 1,4,5-Trisphosphate Receptors genetics metabolism MeSH
- Colorectal Neoplasms genetics metabolism pathology MeSH
- Humans MeSH
- Cell Line, Tumor MeSH
- Breast Neoplasms genetics metabolism pathology MeSH
- Ovarian Neoplasms genetics metabolism pathology MeSH
- Nifedipine pharmacology MeSH
- Cell Movement drug effects genetics MeSH
- Cell Proliferation drug effects genetics MeSH
- Antineoplastic Agents, Immunological pharmacology MeSH
- Sodium-Calcium Exchanger genetics metabolism MeSH
- Receptor, ErbB-2 genetics metabolism MeSH
- Gene Expression Regulation, Neoplastic drug effects MeSH
- RNA Interference MeSH
- Trastuzumab pharmacology MeSH
- Triple Negative Breast Neoplasms genetics metabolism pathology MeSH
- Calcium Signaling drug effects genetics MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Calcium Channel Blockers MeSH
- Inositol 1,4,5-Trisphosphate Receptors MeSH
- Nifedipine MeSH
- Antineoplastic Agents, Immunological MeSH
- Sodium-Calcium Exchanger MeSH
- Receptor, ErbB-2 MeSH
- sodium-calcium exchanger 1 MeSH Browser
- Trastuzumab MeSH
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.
Cancer Research Institute Biomedical Research Center SAS Bratislava Slovakia
Institute of Clinical and Translational Research Biomedical Research Center SAS Bratislava Slovakia
References provided by Crossref.org
