@Article{or.2025.074202,
AUTHOR = {Jo-Yu Lin, Tien-Huang Lin, Ya-Jing Jiang, Liang-Wei Lin, Kuan-Ying Lai, Yi-Chin Fong, Chih-Chuang Liaw, Chih-Hsin Tang},
TITLE = {Ugonin J Inhibits EMT and Migration in Prostate Cancer by Suppressing ADAM9 Expression},
JOURNAL = {Oncology Research},
VOLUME = {34},
YEAR = {2026},
NUMBER = {3},
PAGES = {--},
URL = {http://www.techscience.com/or/v34n3/66282},
ISSN = {1555-3906},
ABSTRACT = { <b>Background:</b> 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 <i>Helminthostachys zeylanica</i>, on PCa metastasis. <b>Methods:</b> 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. <b>Results:</b> 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. <b>Conclusions:</b> Our evidence suggests that Ugonin J is a novel therapeutic candidate for further development as a treatment for metastatic PCa.},
DOI = {10.32604/or.2025.074202}
}