Telomerase Inhibitor TMPyP4 Alters Adhesion and Migration of Breast-Cancer Cells MCF7 and MDA-MB-231
| Autor: | Ewa Toton, Aleksandra Romaniuk-Drapała, Anna Paszel-Jaworska, Natalia Lisiak, Błażej Rubiś, Natalia Konieczna, Mariusz Kaczmarek |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Telomerase
Porphyrins DNA Repair DNA repair Cell Survival MDA-MB-231 telomerase migration Catalysis Article Inorganic Chemistry lcsh:Chemistry breast cancer Cell Movement Cell Line Tumor Cell Adhesion Humans Telomerase reverse transcriptase Physical and Theoretical Chemistry Enzyme Inhibitors Cell adhesion Clonogenic assay Molecular Biology lcsh:QH301-705.5 Spectroscopy TMPyP4 Cell Proliferation Chemistry Organic Chemistry MCF7 Cell Cycle General Medicine Cell cycle MCF-12A Computer Science Applications Telomere Gene Expression Regulation Neoplastic adhesion lcsh:Biology (General) lcsh:QD1-999 Cancer cell Cancer research MCF-7 Cells Female hTERT DNA Damage Signal Transduction |
| Zdroj: | International Journal of Molecular Sciences International Journal of Molecular Sciences, Vol 20, Iss 11, p 2670 (2019) Volume 20 Issue 11 |
| ISSN: | 1422-0067 |
| Popis: | Human telomeres were one of the first discovered and characterized sequences forming quadruplex structures. Association of these structures with oncogenic and tumor suppressor proteins suggests their important role in cancer development and therapy efficacy. Since cationic porphyrin TMPyP4 is known as G-quadruplex stabilizer and telomerase inhibitor, the aim of the study was to analyze the anticancer properties of this compound in two different human breast-cancer MCF7 and MDA-MB-231 cell lines. The cytotoxicity of TMPyP4 alone or in combination with doxorubicin was measured by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromid) and clonogenic assays, and the cell-cycle alterations were analyzed by flow cytometry. Telomerase expression and activity were evaluated using qPCR and telomeric repeat amplification protocol (TRAP) assays, respectively. The contribution of G-quadruplex inhibitor to protein pathways engaged in cell survival, DNA repair, adhesion, and migration was performed using immunodetection. Scratch assay and functional assessment of migration and cell adhesion were also performed. Consequently, it was revealed that in the short term, TMPyP4 neither revealed cytotoxic effect nor sensitized MCF7 and MDA-MB-231 to doxorubicin, but altered breast-cancer cell adhesion and migration. It suggests that TMPyP4 might substantially contribute to a significant decrease in cancer cell dissemination and, consequently, cancer cell survival reduction. Importantly, this effect might not be associated with telomeres or telomerase. |
| Databáze: | OpenAIRE |
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