Dietary garlic has been suggested to possess anticancer properties, and several attempts have been made to isolate the anticancer compounds. In this study, we efficiently synthesized N-benzyl-N-methyl-dodecan-1-amine (BMDA) by the reductive amination method. We evaluated the potential anticancer activities of BMDA against A549 lung cancer cells with cancer stem cell-like phenotypes due to the overexpression of cancer upregulated gene (CUG)2. N-Benzyl-N-methyl-dodecan-1-amine treatment sensitized A549 cells overexpressing CUG2 (A549-CUG2) to apoptosis and autophagy compared with those of the control cells. The treatment with BMDA also reduced tumor development in xenografted nude mice. Furthermore, BMDA inhibited cell migration, invasion, and sphere formation in A549-CUG2 cells, in which TGF-β signaling is involved. Further analysis showed that BMDA hindered TGF-β promoter activity, protein synthesis, and phosphorylation of Smad2, thus decreasing the expression of TGF-β-targeted proteins, including Snail and Twist. N-Benzyl-N-methyl-dodecan-1-amine also decreased Twist expression in vivo. In addition, BMDA inhibited Akt-ERK activities, β-catenin expression, and its transcriptional activity. These results suggest that BMDA can be a promising anticancer agent against cancer cells overexpressing CUG2.
Keywords: CUG2; Garlic; N-benzyl-N-methyl-dodecan-1-amine; Tumor growth factor-β; β-catenin.
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