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Background:Non-small cell lung cancer(NSCLC)is considered one of the leading causes of cancer-related death.Despite the availability of drugs for the treatment of NSCLC,the need for the development of novel agents with high efficiency and fewer adverse effects remains unmet.The natural compound bruceine D(BD)is widely recognized for its notable anti-inflammatory,antiparasitic,and hypoglycemic activities.However,it is unclear whether BD can be used as a novel agent for NSCLC treatment.Materials and Methods:MTT and colony formation assays were used to assess the antiproliferative effect of BD on NSCLC cells.Wound healing and transwell assays were performed to determine the effect of BD on the migration and invasion of H1299 cells,respectively.Western blotting assay was used to detect the expression levels of proteins.Results:We demonstrated that BD significantly inhibited the proliferation of H1299,A549,and H226 cells with respective IC50 values of 6.06 ±0.52,7.15 ±0.90,and 7.21 ± 0.75 μM.In addition,BD suppressed colony formation of H1299 cells in a dose-dependent manner.Following treatment with BD,the migration and invasive capabilities of H1299 cells were significantly inhibited in a dose-and time-dependent manner.Moreover,the results of Western blotting demonstrated that BD treatment resulted in the upregulation of the protein expression of E-cadherin and downregulation of the expression of N-cadherin,twist,snail,integrin αv,integrinβ4,matrix metalloproteinase-7,and β-catenin proteins.Conclusion:BD inhibits proliferation,migration,and invasion of NSCLC cells;therefore,BD may be considered for its potential in adjuvant therapy for NSCLC.