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

Vollständiger Abstract

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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.