# Ugonin J Inhibits EMT and Migration in Prostate Cancer by Suppressing ADAM9 Expression

## TL;DR

Ugonin J, a natural compound, inhibits prostate cancer cell migration and invasion by suppressing ADAM9 and epithelial-mesenchymal transition.

## Contribution

Ugonin J is identified as a novel inhibitor of prostate cancer metastasis through suppression of ADAM9 and EMT pathways.

## Key findings

- Ugonin J blocks migration and invasion in prostate cancer cells without affecting viability.
- Ugonin J suppresses mesenchymal markers and upregulates E-cadherin, indicating inhibition of EMT.
- ADAM9 is the most downregulated ADAM protein following Ugonin J treatment and is linked to metastasis in PCa patients.

## Abstract

Prostate cancer (PCa) is the most prevalent malignancy in men and often correlates with distant metastasis in its advanced stages. The study aimed to investigate the effects of Ugonin J, a natural compound isolated from Helminthostachys zeylanica, on PCa metastasis.

The effects of Ugonin J on cell motility were assessed using migration and invasion assays. Reverse Transcription Quantitative PCR (RT-qPCR) and Western blotting were used to evaluate the impact of Ugonin J on mRNA and protein expression. RNA sequencing (RNA-seq) analysis was performed to investigate candidate mechanisms. Differential gene expression analysis in PCa patients was conducted using multiple databases.

Here, we reveal that Ugonin J blocks migration and invasion in PCa cells without affecting cell viability. RNA-seq analysis suggests that epithelial–mesenchymal transition (EMT) is potentially involved in Ugonin J’s anti-motility effects. Ugonin J also suppresses the expression of mesenchymal markers N-cadherin, β-catenin, Snail, and Slug while upregulating the expression of the epithelial marker E-cadherin. Furthermore, among 13 A disintegrin and metalloproteinase (ADAM) proteins, A disintegrin and metalloproteinase domain-containing protein 9 (ADAM9) is the most downregulated following Ugonin J treatment, according to our RNA-seq data. Importantly, clinical data revealed that ADAM9 expression are higher in PCa patients than in healthy controls and are associated with distant metastasis. Transfection with ADAM9 cDNA reverses Ugonin J-regulated downregulation of EMT, migration, and invasion in PCa cells. Ugonin J inhibits ADAM9-dependent motility by downregulating the phosphoinositide 3-kinase (PI3K), protein kinase B (Akt) and nuclear factor-κB (NF-κB) pathways.

Our evidence suggests that Ugonin J is a novel therapeutic candidate for further development as a treatment for metastatic PCa.