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

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 (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.

Anti-tumor pharmacology of natural products targeting mitosis

“…Therefore, the mechanism underlying garcinol-induced cell cycle arrest requires further investigation. Similar G1 arrest by 13-O-acetylsolstitialin A and Tetrandrine has been observed, both of which act on the cyclin D1-CDK4 complex: 13-O-acetylsolstitialin A decreases the expression of cyclin D1 and CDK4 156 , whereas Tetrandrine binds the cyclin D1-CDK4 complex and forms hydrogen bonds 157 .…”

Brevilaterin B from Brevibacillus laterosporus has selective antitumor activity and induces apoptosis in epidermal cancer

“…Additionally, the mitochondrion is the "factory" for ROS release, which is the rst important feature for apoptosis evaluation. On stimulation from an external factor, intracellular ROS levels can be increased substantially, which can cause oxidative damage to the cell membrane, proteins, and nucleic acids, until apoptosis occurs (Shahrestanaki et al 2019). In the present study, a 10-fold increase in the amount of ROS released was observed when the concentration of Brevilaterin B was increased from 2 to 3 µg/mL.…”

A Marine Alkaloid, Ascomylactam A, Suppresses Lung Tumorigenesis via Inducing Cell Cycle G1/S Arrest through ROS/Akt/Rb Pathway

“…Accumulating studies have reported that various natural products exhibited powerful antitumor effects by the generation of ROS with their pro-oxidative activities [ 14 , 15 , 16 ]. In our investigation, the intracellular ROS production in the lung cancer cells was measured after treatment of AsA.…”