Oleuropein: A Potential Inhibitor for Prostate Cancer Cell Motility by Blocking Voltage-Gated Sodium Channels

Abstract

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.

Acknowledgments

The authors would like to thank Professor Seyhan ALTUN, PhD (Molecular Biology and Genetic Department, Faculty of Science and Arts, Istanbul Kültür University) for gifting the MAT-LyLu cell line.

Conflict of Interest

Hatice Gumushan Aktas declares that pending a patent (Turkish Patent and Trademark Office, application no: 2019/18799) on the ability of olive leaves and oleuropein to block VGSCs and to be an antimetastatic agent. Huda Ayan declares that have no conflict of interest.

Ethical Approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed Consent

For this type of study, formal consent is not required.

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Author Contributions

Hatice Gumushan Aktas conceived the study and the experimental design, performed cell culture experiments with Olive leaf extract, conducted molecular analyses, and wrote the paper. Huda Ayan handled cell culture assays with Oleuropein.

Additional information

Funding

The work was partially supported by the Harran University Scientific Research Projects Coordinatorship (HUBAP; grant no.: 17065), Sanliurfa, Turkey.