Teucrium polium plant extract inhibits cell invasion and motility of human prostate cancer cells via the restoration of the E-cadherin/catenin complex.

Prostate cancer is the first most common malignancy in men worldwide; this cancer is characterized by a marked propensity for invasion and spreading to local lymph nodes. On the other hand, Teucrium polium (TP) is a medicinal plant that has been used for more than two thousand years for treating many diseases such as abdominal pain, indigestion and diabetes in the Middle East. However, the effect of TP plant extract on human metastatic cancer cells especially prostate has not been investigated yet. In this study, we examined the effects of TP extract on selected parameters in PC3 and DU145 prostate cancer cell lines. Our results show that TP plant extract inhibits cell proliferation and provokes S cell cycle arrest and reduction of G0-G1 phase. In parallel, this extract induces differentiation to an epithelial phenotype "mesenchymal-epithelial transition" which is an important event in cell invasion and metastasis; thus TP plant extract causes a dramatic decrease in cell invasion and motility abilities of PC3 and DU145 cancer cells in comparison with untreated cells. These changes are accompanied by a re-localization of the expression patterns of E-cadherin and catenins. The molecular pathway analysis of the TP plant extract revealed that it inhibits the phosphorylation of beta-catenin, via Src dephosphorylation, and consequently converts its role from a transcriptional regulator to a cell-cell adhesion molecule. Our findings indicate that TP plant extract inhibits signaling pathways involved in regulating the E-cadherin/catenin complex and possibly other cell-cell adhesion genes via beta-catenin alteration, suggesting that this plant extract has therapeutic promise in the treatment of human metastatic prostate cancer.