Benzoxazine Dimer Analogue Targets Integrin ß3 in Lung Cancer Cells and Suppresses Anoikis Resistance and Migration.

ABSTRACT

BACKGROUND/AIM: Certain integrins including integrin ß3 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 ß3 and its related downstream proteins including active focal adhesion kinase (FAK) and active protein kinase B (AKT); however, integrin ß1 and α5 were found to be unaltered. CONCLUSION: HM shows a potential in targeting integrin ß3 and could be a good candidate for further developed as an anti-metastatic therapy.