Telmisartan anti-cancer activities mechanism through targeting N-cadherin by mimicking ADH-1 function

This study aimed to investigate if Telmisartan as a novel N-Cadherin antagonist, can overcome cell migration of Cancer cells. We investigated the mechanism and influence of Docetaxel and Telmisartan (as an analogous to ADH-1, which is a well-known N-Cadherin antagonist) on Cancer cells. The effect of ADH-1 and Telmisartan on cell attachment in PC3, DU145, MDA-MB-468 cell lines using recombinant human N-Cadherin was studied. Cell viability assay was performed to examine the anti-proliferative effects of Telmisartan, ADH-1 and Docetaxel. Migration was examined via wound healing assay, and Apoptosis was determined by flow cytometry. The expression of AKT-1 as a downstream gene of N-Cadherin signalling pathway was assayed by Real-Time PCR. Treatment of PC3, MDA-MB-468 and DU145 cells with Telmisartan (0.1 µM) and ADH-1 (40 µM) resulted in 50%, 58% and approximately 20% reduction in cell attachment to N-Cadherin coated plate respectively. It shows reduction of cell attachment in PC3 and MDA-MB-468 cell lines appeared to be more sensitive than that of DU145 cells to the Telmisartan and ADH-1 treatments. Telmisartan (0.1 µM) and Docetaxel (0.01 nM) significantly reduced cell migration in PC3 and MDA-MB-468 cell lines compared with the control group. Using Real-Time PCR, we found that Telmisartan, Docetaxel and ADH-1 had significant influence on the AKT-1 mRNA level. The results of the current study for the first time suggest that, Telmisartan, exerts anti-proliferation and anti-migration effects by targeting antagonistically N-Cadherin. Also, these data suggest that Telmisartan as a less expensive alternative to ADH-1 could potentiate Docetaxel Anticancer effects.