Centaurea cyanus extracted 13‐O‐acetylsolstitialin A decrease Bax/Bcl‐2 ratio and expression of cyclin D1/Cdk‐4 to induce apoptosis and cell cycle arrest in MCF‐7 and MDA‐MB‐231 breast cancer cell lines
| Autor: | Seyyed Mehdi Jafari, Mahboobeh Bagheri, Mohammad Keyvanloo Shahrestanaki, Mustafa Ghanadian, Mahmoud Aghaei |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Programmed cell death Cell cycle checkpoint Cell Survival Antineoplastic Agents Apoptosis Breast Neoplasms Centaurea Biochemistry Lactones 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cyclin D1 Annexin Cyclin-dependent kinase Cell Line Tumor Humans Propidium iodide Molecular Biology bcl-2-Associated X Protein Membrane Potential Mitochondrial Molecular Structure biology Plant Extracts Cyclin-Dependent Kinase 4 Cell Biology G1 Phase Cell Cycle Checkpoints Molecular biology 030104 developmental biology Proto-Oncogene Proteins c-bcl-2 MCF-7 chemistry 030220 oncology & carcinogenesis MCF-7 Cells biology.protein Reactive Oxygen Species Sesquiterpenes |
| Zdroj: | Journal of Cellular Biochemistry. 120:18309-18319 |
| ISSN: | 1097-4644 0730-2312 |
| DOI: | 10.1002/jcb.29141 |
| Popis: | Natural products are considered recently as one of the source for production of efficient therapeutical agents for breast cancer treatment. In this study, a sesquiterpene lactone, 13-O-acetylsolstitialin A (13ASA), isolated from Centaurea cyanus, showed cytotoxic activities against MCF-7 and MDA-MB-231 breast cancer cell lines using standard 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. To find the mechanism of action of cytotoxicity, annexin V/propidium iodide (PI) staining was performed for evaluation of apoptosis. This process was further confirmed by immunoblotting of anti- and proapoptotic, Bcl-2 and Bax, proteins. Cell cycle arrest was evaluated by measurement of fluorescence intensity of PI dye and further confirmed by immunoblotting of Cdk-4 and cyclin D1. Mitochondrial transmembrane potential (ΔΨm) and generation of reactive oxygen species (ROS) were measured using the JC-1 and DCFDA fluorescence probes, respectively. These experiments showed that 13ASA is a potent cytotoxic agent, which activates apoptosis-mediated cell death. In response to this compound, Bax/Bcl-2 ratio was noticeably increased in MCF-7 and MDA-MB-231 cells. Moreover, 13ASA induced cell cycle arrest at subG1 and G1 phases by decreasing protein levels of cyclin D1 and Cdk-4. It was done possibly through the decrease of ΔΨm and increase of ROS levels which induce apoptosis. In conclusion, this study mentioned that 13ASA inhibit the growth of MCF-7 and MDA-MB-231 breast cancer cell lines through the induction of cell cycle arrest, which triggers apoptotic pathways. 13ASA can be considered as a susceptible compound for further investigation in breast cancer study. |
| Databáze: | OpenAIRE |
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