Magnocurarine inhibits migration and invasion by suppressing mesenchymal marker expression and MAPK signaling in castration-resistant prostate cancer cells.

Background

Magnocurarine is an alkaloid isolated from several traditional Asian medicinal plants, including Magnolia and Harrisonia species. Previous studies have reported its anti-nociceptive, anti-inflammatory, and antimicrobial activities with relatively low cytotoxicity. However, the anticancer activity of magnocurarine, particularly its effects on prostate cancer cell migration and invasion, has not been well characterized.

Objective

This study aims to investigate the effects of magnocurarine on the migration and invasion of castration-resistant prostate cancer (CRPC) cells.

Methods

DU145 and PC3 cells were treated with non-toxic concentrations of magnocurarine (0-40 µM), and migration and invasion capabilities were evaluated using scratch wound healing and transwell invasion assays, gelatin zymography, and western blot analysis.

Results

Magnocurarine significantly reduced the migration and invasion of CRPC cells in a dose-dependent manner (p < 0.05). The inhibitory effects were associated with decreased activities of MMP-2 and MMP-9, together with reduced expression of invasion-related proteins including uPA, uPAR, and MT1-MMP. In addition, magnocurarine suppressed the expression of mesenchymal markers, including N-cadherin, vimentin, and fibronectin. Further investigation showed that magnocurarine decreased the phosphorylation of ERK, JNK, and p38 without altering total protein expression, suggesting suppression of MAPK signaling activation.

Conclusion

These findings indicate that magnocurarine attenuates migratory and invasive phenotypes in CRPC cells and is associated with reduced activation of MAPK signaling. This study provides initial evidence supporting the anti-migratory and anti-invasive effects of magnocurarine in prostate cancer cells and suggests its potential for further investigation as a phytochemical-derived drug candidate in advanced prostate cancer.