PMID:
Mol Nutr Food Res. 2020 Jan 24:e1900390. Epub 2020 Jan 24. PMID: 31976617
Abstract Title:
Gut metabolite, Urolithin A decreases Actin Polymerization and Migration in Cancer Cells.
Abstract:
SCOPE: Urolithin A (UA) is a gut-derived metabolite from ellagic acid found in pomegranates, berries and nuts can down-regulate cell proliferation and migration. Cell proliferation and cell motility require actin reorganization which is under control of ras-related C3 botulinum toxin substrate 1 (Rac1) and p21 protein-activated kinase 1 (PAK1). The present study explored whether Urolithin A can modify actin cytoskeleton in cancer cells.METHODS: The effect of Urolithin A on globular over filamentous actin ratio was determined utilizing Western blotting, immunofluorescence and flow cytometry. Rac1 and PAK1 levels were measured by qRT-PCR and immunoblotting. As a result, a 24 hour treatment with Urolithin A (20μM) significantly decreased Rac1 and PAK1 transcript levels and activity, depolymerized actin and wound healing. The effect of Urolithin A on actin polymerization was mimicked by pharmacological inhibition of Rac1 and PAK1. The effect was also mirrored by knock down using siRNA.CONCLUSION: Urolithin A leads to disruption of Rac1 and Pak1 activity with subsequent actin depolymerization and migration. Thus, use of dietary Urolithin A in cancer prevention or as adjuvant therapy is promising. This article is protected by copyright. All rights reserved.
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