22-O-(N-Boc-l-glycine) ester of renieramycin M inhibits migratory activity and suppresses epithelial –mesenchymal transition in human lung cancer cells

In this study, the effect of 22-O-(N-Boc-l-glycine) ester of renieramycin M (22-Boc-Gly-RM), a semi-synthetic amino ester derivative of bistetrahydroisoquinolinequinone alkaloid isolated fromXestospongia sp., on migratory behavior of human lung cancer cells was investigated. Following 24  h of treatment, 22-Boc-Gly-RM at non-toxic concentrations (0.5–1 μM) effectively restrained motility of human lung cancer H460 cells assessed through wound healing, transwell migration, and multicellular spheroid models. The capability to invade through matrix component was also repressed in H 460 cells cultured with 0.1–1 µM 22-Boc-Gly-RM. The dose-dependent reduction of phalloidin-stained actin stress fibers corresponded with the downregulated Rac1-GTP level presented via western blot analysis in 22-Boc-Gly-RM-treated cells. Treatment with 0.1–1 μM of 22-Boc-Gly-RM obviously cau sed suppression of p-FAK/p-Akt signal and consequent inhibition of epithelial-to-mesenchymal transition (EMT), which was evidenced with augmented level of E-cadherin and reduction of N-cadherin expression. The alteration of invasion-related proteins in 22-Boc-Gly-RM-treated H460 cells was indicated by the diminution of matrix metalloproteinases (MT1-MMP, MMP-2, MMP-7, and MMP-9), as well as the upregulation of tissue inhibitors of metalloproteinases (TIMP), TIMP2, and TIMP3. Thus, 22-Boc-Gly-RM is a promising candidate for anti-metastasis treatment in lung cancer through inhibition of migrator y featur...
Source: Journal of Natural Medicines - Category: Drugs & Pharmacology Source Type: research