In this study, we investigated whether olive leaf and oleuropein have the potential to stop cell motility, which a metastatic cell behavior by blocking voltage-gated sodium channels (VGSCs). For this purpose, it was first prepared the aqueous extract of olive leaves (AOLE). Then it was assayed the effect on the motility of MAT-LyLu, a highly metastatic Dunning rat prostate adenocarcinoma cells of this extract. The phenolic content of AOLE was analyzed using LC-MS/MS instrument. It was observed that oleuropein was the most finding compound in AOLE. Therefore, whether oleuropein was responsible for the inhibitory effect of AOLE on the MAT-LyLu cell movement was tested. Nontoxic oleuropein concentrations and those that did not affect proliferation on MAT-LyLu cells were determined. Subsequently, it was examined the effects of oleuropein on the lateral and vertical movement of MAT-LyLu cells. To elucidate the mechanism of oleuropein affecting cell motility, whether it suppressed mRNA expression of SCN9A, which encodes the VGSC was analyzed. Accordingly, oleuropein suppressed the movement of MAT-LyLu cells by reducing SCN9A mRNA expression. In conclusion, we report the first time that oleuropein might be considered as a potential antimetastatic agent for prostate cancer due to its blocking effect on VGSC-mediated cell motility.

Hedera helix L., a member of Araliaceae family, has antiproliferative, cytotoxic, antimicrobial, antifungal, antiprotozoal and anti‑inflammatory effects, and is used in cosmetics. The aim of the present study was to investigate the effect of treatment with extracts of leaves and unripened fruits of H. helix on rat prostate cancer cell lines with markedly different metastatic potentials: Mat‑LyLu cells (strongly metastatic) and AT‑2 cells (weakly metastatic). The effects of the extracts on cell kinetics and migration were determined. Tetrodotoxin was used to block the voltage‑gated sodium channels (VGSCs) associated specifically with Mat‑LyLu cells. Cell proliferation was detected spectrophotometrically using the 3-(4,5-dimethyl‑2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay. The mitotic index was determined using the Feulgen staining method. Lateral motility was quantified by wound‑healing assays. The results of the present study demonstrated that cell kinetics (proliferation and mitotic activity) and motility were inhibited by ethanolic leaf extract of H. helix. The ethanolic extract of H. helix fruit suppressed Mat‑LyLu cell migration, with no effect on proliferation. The opposite effects were observed in AT‑2 cells; migration was not affected but proliferation was inhibited. In conclusion, the ethanolic fruit extract of H. helix may inhibit the cell migration of Mat‑LyLu cells by blocking VGSCs. However, the effect of ethanolic leaf extract of H. helix treatment on the lateral motility of the cancer cells is unclear.