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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

Keyvanloo Shahrestanaki, M. and Bagheri, M. and Ghanadian, M. and Aghaei, M. and Jafari, S.M. (2019) 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. Journal of Cellular Biochemistry, 120 (10). pp. 18309-18319.

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Abstract

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 (�Ψm) 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 �Ψm 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. © 2019 Wiley Periodicals, Inc.

Item Type: Article
Additional Information: cited By 0
Uncontrolled Keywords: 13 o acetylsolstitialin; cyclin D1; cyclin dependent kinase 4; cytotoxic agent; fluorescent dye; lipocortin 5; plant extract; propidium iodide; protein Bax; protein bcl 2; reactive oxygen metabolite; sesquiterpene lactone; unclassified drug, antiproliferative activity; apoptosis; Article; breast cancer; cell cycle arrest; cell death; cell viability; Centaurea; Centaurea cyanus; clinical evaluation; cytotoxicity; drug isolation; drug mechanism; fluorescence analysis; G1 phase cell cycle checkpoint; human; human cell; immunoblotting; MCF-7 cell line; MDA-MB-231 cell line; membrane potential; mitochondrial membrane; MTS assay; priority journal; protein expression; staining; transepithelial potential difference
Subjects: بیماریهای زنان WP
QU بیوشیمی
آسیب شناسی QZ
مقالات نمایه شده محققین دانشگاه در سایت ,Web of Science ,Scopus
Divisions: معاونت تحقیقات و فناوری
Depositing User: GOUMS
Date Deposited: 16 Dec 2019 11:14
Last Modified: 16 Dec 2019 11:14
URI: http://eprints.goums.ac.ir/id/eprint/10432

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