ADH-10001

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.

Induced pluripotent stem cells (iPSCs) hold promise in revolutionizing medicine; however, their application potential is limited because of low reprogramming efficiency. Mesenchymal-to-epithelial transition (MET) has been proved to involve reprogramming of somatic cells into iPSCs, making it a promising target for enhancing generation of iPSCs. Here, we nanoengineered N-cadherin-blocking peptide ADH-1 with gold nanoparticles, generating a multivalent N-cadherin antagonist (ADH-AuNPs), for improving reprogramming efficiency through driving cell MET. ADH-AuNPs exhibited good biocompatibility and showed higher N-cadherin inhibitory activity than ADH-1 due to multivalency, thereby enhancing cell-state reprogramming toward epithelial lineages. Particularly, ADH-AuNPs improved reprogramming efficiency by more than 7-fold after introduction of four Yamanaka factors. Importantly, ADH-AuNPs generated iPSCs displayed high stemness and pluripotency in vitro and in vivo. Therefore, we provide a cooperative strategy for promoting the iPSC generation efficacy.