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Updated: Mar 10, 2026
An Orthotopic Murine Model of Human Prostate Cancer Metastasis
Published on: September 18, 2013
Ugonin J Inhibits EMT and Migration in Prostate Cancer by Suppressing ADAM9 Expression
Jo-Yu Lin1, Tien-Huang Lin2,3, Ya-Jing Jiang4
1Graduate Institute of Biomedical Sciences, China Medical University, Taichung, 404333, Taiwan.
Background:
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.
Methods:
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.
Results:
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.
Conclusions:
Our evidence suggests that Ugonin J is a novel therapeutic candidate for further development as a treatment for metastatic PCa.
Insights
Ugonin J, a natural compound, effectively inhibits prostate cancer (PCa) metastasis by targeting epithelial-mesenchymal transition (EMT) and ADAM9. This discovery offers a promising new therapeutic avenue for advanced PCa treatment.
Area of Science:
- Oncology
- Natural Product Chemistry
- Molecular Biology
Background:
- Prostate cancer (PCa) is a prevalent malignancy often associated with distant metastasis in advanced stages.
- Investigating natural compounds for anti-metastatic properties is crucial for developing novel cancer therapies.
Purpose of the Study:
- To evaluate the anti-metastatic effects of Ugonin J, a compound from *Helminthostachys zeylanica*, on prostate cancer.
- To elucidate the molecular mechanisms underlying Ugonin J's action on PCa cell motility.
Main Methods:
- Cell migration and invasion assays were employed to assess Ugonin J's impact on PCa cell motility.
- Reverse Transcription Quantitative PCR (RT-qPCR), Western blotting, and RNA sequencing (RNA-seq) were used to analyze gene and protein expression changes.
- Clinical data analysis was performed using multiple databases to correlate gene expression with PCa patient outcomes.
Main Results:
- Ugonin J significantly inhibited PCa cell migration and invasion without affecting cell viability.
- RNA-seq data indicated that Ugonin J suppresses epithelial-mesenchymal transition (EMT) by downregulating mesenchymal markers (N-cadherin, β-catenin, Snail, Slug) and upregulating E-cadherin.
- Ugonin J downregulated ADAM9 expression, a protein found to be upregulated in PCa patients and associated with metastasis. Overexpression of ADAM9 reversed Ugonin J's anti-motility effects, highlighting ADAM9's role in PCa metastasis.
- Ugonin J inhibits ADAM9-dependent motility via the PI3K/Akt and NF-κB pathways.
Conclusions:
- Ugonin J demonstrates significant anti-metastatic activity in prostate cancer models.
- The compound acts by suppressing EMT and downregulating ADAM9, a key mediator of PCa metastasis.
- Ugonin J represents a promising therapeutic candidate for the treatment of metastatic prostate cancer.
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Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...