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

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.