Anticancer effect of Dracaena arborea leaf extract through down-regulation of VCAM-1 and EMT proteins via suppressing Akt/PKC pathway

Abstract

Dracaena arborea (Willd.) Link is known to be used in traditional medicine for the treatment of various diseases. Because it possesses steroidal saponins and flavonoids which display a variety of biological actions including anti-carcinogenic,it might exhibit anti-cancer effect. However, the anti-cancer effect of D. arborea is not well known. Therefore,in this study, we investigated anti-cancer effect of D. arborea on highly metastatic human breast cancer cells MDA-MB-231. Methanolic extract of leaves of Dracaena arborea (MEDA) decreased cell viability of MDA-MB-231 cells, but not endothelialcells (ECs), in a dose-dependent manner for 24 h. Then, pretreatment of MEDA significantly inhibited the binding of MDAMB-231 to ECs and the invasion of MDA-MB-231 in the presence of tumor necrosis factor (TNF)-α or not. Pretreatmentof MEDA significantly inhibited vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) expression both in TNF-α-treated MDA-MB-231 cells and ECs at the indicated doses, and the inhibitory effect was moreprominent in VCAM-1 rather than ICAM-1. TNF-α-mediated induction of β-catenin and Snail-1 and secretion of matrixmetalloproteinase-9 (MMP-9) were significantly down-regulated by MEDA from 50 μg/ml and 100 μg/ml, respectively. Furthermore,MEDA effectively down-regulated protein kinase C (PKC) and Akt activation by TNF-α, suggesting that inhibitionof PKC and Akt pathways by MEDA are responsible for differential inhibition of VCAM-1 and the epithelial–mesenchymal transition (EMT)-related proteins β-catenin and Snail-1. Taken together, MEDA exhibits anti-cancer effectsthrough inhibition of adhesion of cancer cells to ECs and the invasion of cancer cells through down-regulation of VCAM-1 and EMT proteins via suppressing Akt/PKC pathway, suggesting a possibility to be served as a therapeutic agent againstcancer metastasis.