ISSN: 2574-187X
Authors: Samantaray A†, Pradhan D*, Nayak NR, Behera B and Mohanty L
Aim: To investigate the effects of Tupichinol E, an alkaloid present in Tupistra chinensis BAKER (Liliaceae) on the metastasis of Triple negative mammary carcinoma in-vitro, and elucidate the underlying mechanisms and Tupichinol E binding to EGFR stabilises the protein structure and is a pharmacologically active substance that can be used against cancer due to its potent activity. Methods: Growth of MCF-7 and MDA-MB-231 cells was assessed using MTT assay. Apoptosis and cell cycle of MCF-7 cells were evaluated with flow cytometry, and the related proteins were examined using Western blotting. Structurally similar EGFR inhibitors, their modes of binding and mechanism of actions are a new way to select lead compounds for better alternatives. Therefore molecular docking is done to find a potential anti-EGFR flavonoid. Results: Tupichinol E (35–280 μmol/L) inhibited the growth of MCF-7 cells in time- and dose-dependent manners (the IC50 values were 105±1.08 and 78.52±1.06 μmol/L, respectively, at 48 and 72 h). Treatment of MCF-7 cells with Tupichinol E (70–280 μmol/L) dose-dependently induced apoptosis of MCF-7 cells, accompanying activation of caspase 3. The cells treated with Tupichinol E (140 and 280 μmol/L) significantly increased the percentage of cells in G2/M phase with a reduction in the expression of cyclin B1. Osmertinib shows binding energy -107.23 kcal/mol with EGFR, while Tupichinol E shows binding energy -98.89 kcal/mol. Tupichinol E shows 1.5 times more binding affinity than Osmertinib. Conclusion: These results demonstrated that Tupichinol E is an effective antitumor compound in vitro and in-silico, and has the potential to be developed as a new anticancer drug.
Keywords: Molecular Docking; Tupichinol E; MCF-7; MDA-MB-231; Flow Cytometry; Western Blotting; MTT Assay
