Gut Bacterial Metabolite Urolithin A Decreases Actin Polymerization and Migration in Cancer Cells

肠道细菌代谢物尿石素 A 降低癌细胞中的肌动蛋白聚合和迁移

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作者:Md Alauddin, Toshiyuki Okumura, Janet Rajaxavier, Shayan Khozooei, Simone Pöschel, Satoru Takeda, Yogesh Singh, Sara Y Brucker, Diethelm Wallwiener, André Koch, Madhuri S Salker

Conclusion

UA leads to disruption of Rac1 and Pak1 activity with subsequent actin depolymerization and migration. Thus, use of dietary UA in cancer prevention or as adjuvant therapy is promising.

Methods

The effect of UA on globular over filamentous actin ratio is determined utilizing Western blotting, immunofluorescence, and flow cytometry. Rac1 and PAK1 levels are measured by quantitative RT-PCR and immunoblotting. As a result, a 24 h treatment with UA (20 µm) significantly decreased Rac1 and PAK1 transcript levels and activity, depolymerized actin and wound healing. The effect of UA on actin polymerization is mimicked by pharmacological inhibition of Rac1 and PAK1. The effect is also mirrored by knock down using siRNA.

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