Inhibition of A549 Lung Cancer Cell Migration and Invasion by Ent -Caprolactin C via the Suppression of Transforming Growth Factor-β-Induced Epithelial-Mesenchymal Transition

The epithelial-mesenchymal transition (EMT) of cancer cells is a crucial process in cancer cell metastasis. An sp. MC085 extract was found to inhibit A549 human lung cancer cell invasion, and caprolactin C ( ), a new natural product, α-amino-ε-caprolactam linked to 3-methyl butanoic acid, was purified through bioactivity-guided isolation of the extract. Furthermore, its enantiomeric compound, -caprolactin C ( ), was synthesized. Both and inhibited the invasion and γ-irradiation-induced migration of A549 cells. In transforming growth factor-β (TGF-β)-treated A549 cells, inhibited the phosphorylation of Smad2/3 and suppressed the EMT cell marker proteins (N-cadherin, β-catenin, and vimentin), as well as the related messenger ribonucleic acid expression (N-cadherin, matrix metalloproteinase-9, Snail, and vimentin), while compound did not suppress Smad2/3 phosphorylation and the expression of EMT cell markers. Therefore, compound could be a potential candidate for antimetastatic agent development, because it suppresses TGF-β-induced EMT.