RESUMO
BACKGROUND/AIM: Enhanced cell motility is a hallmark of highly metastatic cancer cells. The anti-migratory activity of Dendrofalconerol A (DF-A), a pure bis(bibenzyls) isolated from the stem of Dendrobium falconeri (Orchidaceae) is reported in the present study. MATERIALS AND METHODS: Cytotoxicity effects of DF-A on H460 lung cancer cells was determined by the MTT assay. We also investigated the mechanism of DF-A-mediated EMT and integrin proteins level by western blotting. RESULTS: DF-A at concentrations of 0.5-5 µM significantly reduced the protein level of migrating cells in a dose-dependent manner. The expression of migration-related integrins, including integrin ß1 and integrin α4 was significantly reduced in response to DF-A treatment. Also, DF-A was shown to suppress epithelial to mesenchymal transition (EMT), as indicated by cadherin switch from N- to E-cadherin and decrease of Snail, Slug and vimentin. CONCLUSION: This study revealed the potential of DF-A, an anti-metastasis agent and the underlying mechanism in this in vitro assay with H460 cells, which leads to the development of a novel anti-metastatic agent.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Bibenzilas/farmacologia , Movimento Celular/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Integrina alfa1/metabolismo , Integrina beta4/metabolismo , Xantenos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , HumanosRESUMO
Resistance to anoikis, enhanced cell motility, and growth in anchorage-independent conditions are hallmarks of highly metastatic cancer cells. The present study demonstrates the anoikis-sensitizing and anti-migration activities of dendrofalconerol A (DF-A), a pure bis(bibenzyl) isolated from the stem of Dendrobium falconeri (Orchidaceae), and its underlying mechanisms in human lung cancer H460 cells. DF-A at non-toxic concentrations significantly increased the anoikis response of the cancer cells, but caused no toxic effect on normal keratinocytes. In addition, DF-A significantly inhibited the growth of lung cancer cells in anchorage-independent conditions. Western blot analysis revealed that the anoikis-sensitizing effect of such a compound involves its ability to suppress survival signals as well as anti-apoptotic proteins, namely, activated protein kinase B (Akt) and Bcl-2. Furthermore, DF-A decreased caveolin-1 (Cav-1), a protein responsible for aggressiveness, while having no effect on Bax, Mcl-1, and activated Erk (p42/44) proteins. In the case of cell motility, DF-A exhibited strong anti-migration activity with the mechanism involving suppression of pFAK and Rho-GTP, but had no effect on Rac-GTP in lung cancer cells. Taken together, DF-A possesses anoikis-sensitizing activity along with anti-migration effects, and may be developed as a novel active compound for cancer treatment.