A Bibenzyl from Dendrobium ellipsophyllum inhibits epithelial-to-mesenchymal transition and sensitizes lung cancer cells to anoikis.

BACKGROUND

Anti-metastasis therapy may become the potential means of improving survival of cancer patients. As the ability of cancer cells to change phenotype from epithelial to mesenchymal has been recognized as an important hallmark of cancer metastasis, this study provides information regarding the effect of a bibenzyl, namely 4,5,4'-trihydroxy-3,3'-dimethoxybibenzyl (TDB), isolated from Dendrobium ellipsophyllum, in inhibiting epithelial-to-mesenchymal transition (EMT) and sensitization of lung cancer cells to anoikis.

METHODS

Human lung cancer H292 cells were treated with non-cytotoxic doses of TDB for 24 h prior to evaluation of anoikis and anchorage-independent growth. The proteins relevant to EMT and anoikis resistance were examined in TDB-treated H292 cells via western blot analysis.

RESULTS

A significant increase in apoptosis induced by cell detachment was found in TDB-treated H292 cells. The formation of tumor in anchorage-independent growth assay was found to be dramatically reduced in response to the compound. Furthermore, western blot analysis of proteins involved in EMT revealed that treatment with TDB resulted in the increase of E-cadherin and the decrease of vimentin and transcription factor SNAIL, indicating EMT suppression. Concomitantly with EMT inhibition, the activity of pro-survival pathways, including activated protein kinase B (pAKT) and activated extracellular signal-regulated kinase (pERK), were found to be significantly reduced.

CONCLUSIONS

Because EMT, anoikis resistance and anchorage-independent growth are among important factors facilitating cancer metastasis, TDB shows potential to be developed as an anti-metastasis agent.