Benzoxazine Dimer Analogue Targets Integrin β3 in Lung Cancer Cells and Suppresses Anoikis Resistance and Migration

Background/Aim: Certain integrins including integrin beta 3 facilitate movement and survival of metastatic cancer cells. We examined whether benzoxazine dimer analogue N,N-bis(5-ethyl-2-hydroxybenzyl) methylamine (HM) has anti-metastatic effects. Materials and Methods: Cell viability was examined by the 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) assay. Wound healing and phalloidin-rhodamine assays were performed to evaluate the migration and filopodia formation, respectively. Anoikis resistance was studied by anchorage-independent growth assay. The expression of proteins regulating migration were examined by western blot. Results: HM treatment significantly inhibited growth and survival of detached lung cancer cells as indicated by the reduced colony number and size of anchorage-independent growth analysis. HM inhibited cell migration and suppressed filopodia formation. Protein analysis indicated that the compound dramatically decreased integrin beta 3 and its related downstream proteins including active focal adhesion kinase (FAK) and active protein kinase B (AKT); however, integrin beta 1 and alpha 5 were found to be unaltered. Conclusion: HM shows a potential in targeting integrin beta 3 and could be a good candidate for further developed as an anti-metastatic therapy.